var bibbase_data = {"data":"<img src=\"//bibbase.org/img/ajax-loader.gif\" id=\"spinner\"\n  style=\"display: none;\" alt=\"Loading..\" />\n\n<div id=\"bibbase\">\n\n  <script type=\"text/javascript\">\n    var bibbase = {\n      params: {\"jsonp\":\"1\",\"host\":\"bibbase.org\"},\n      data: [{\"title\":\"VIOLIN: vaccine investigation and online information network\",\"type\":\"article\",\"year\":\"2007\",\"keywords\":\"database\",\"pages\":\"D923-D928\",\"volume\":\"36\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/18025042,https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm1039\",\"month\":\"12\",\"day\":\"23\",\"id\":\"ac4d6ece-2838-3f27-bb85-0d27f2ac0bf7\",\"created\":\"2009-08-22T08:04:52.000Z\",\"accessed\":\"2011-05-21\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2018-02-17T12:57:12.685Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Xiang2008\",\"private_publication\":false,\"abstract\":\"Vaccines are among the most efficacious and cost-effective tools for reducing morbidity and mortality caused by infectious diseases. The vaccine investigation and online information network (VIOLIN) is a web-based central resource, allowing easy curation, comparison and analysis of vaccine-related research data across various human pathogens (e.g. Haemophilus influenzae, human immunodeficiency virus (HIV) and Plasmodium falciparum) of medical importance and across humans, other natural hosts and laboratory animals. Vaccine-related peer-reviewed literature data have been downloaded into the database from PubMed and are searchable through various literature search programs. Vaccine data are also annotated, edited and submitted to the database through a web-based interactive system that integrates efficient computational literature mining and accurate manual curation. Curated information includes general microbial pathogenesis and host protective immunity, vaccine preparation and characteristics, stimulated host responses after vaccination and protection efficacy after challenge. Vaccine-related pathogen and host genes are also annotated and available for searching through customized BLAST programs. All VIOLIN data are available for download in an eXtensible Markup Language (XML)-based data exchange format. VIOLIN is expected to become a centralized source of vaccine information and to provide investigators in basic and clinical sciences with curated data and bioinformatics tools for vaccine research and development. VIOLIN is publicly available at http://www.violinet.org.\",\"bibtype\":\"article\",\"author\":\"Xiang, Zuoshuang and Todd, Thomas and Ku, Kim P and Kovacic, Bethany L and Larson, Charles B and Chen, Fang and Hodges, Andrew P and Tian, Yuying and Olenzek, Elizabeth A and Zhao, Boyang and Colby, Lesley A and Rush, Howard G and Gilsdorf, Janet R and Jourdian, George W and He, Yongqun\",\"doi\":\"10.1093/nar/gkm1039\",\"journal\":\"Nucleic Acids Research\",\"number\":\"Database\",\"bibtex\":\"@article{\\n title = {VIOLIN: vaccine investigation and online information network},\\n type = {article},\\n year = {2007},\\n keywords = {database},\\n pages = {D923-D928},\\n volume = {36},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/18025042,https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm1039},\\n month = {12},\\n day = {23},\\n id = {ac4d6ece-2838-3f27-bb85-0d27f2ac0bf7},\\n created = {2009-08-22T08:04:52.000Z},\\n accessed = {2011-05-21},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2018-02-17T12:57:12.685Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Xiang2008},\\n private_publication = {false},\\n abstract = {Vaccines are among the most efficacious and cost-effective tools for reducing morbidity and mortality caused by infectious diseases. The vaccine investigation and online information network (VIOLIN) is a web-based central resource, allowing easy curation, comparison and analysis of vaccine-related research data across various human pathogens (e.g. Haemophilus influenzae, human immunodeficiency virus (HIV) and Plasmodium falciparum) of medical importance and across humans, other natural hosts and laboratory animals. Vaccine-related peer-reviewed literature data have been downloaded into the database from PubMed and are searchable through various literature search programs. Vaccine data are also annotated, edited and submitted to the database through a web-based interactive system that integrates efficient computational literature mining and accurate manual curation. Curated information includes general microbial pathogenesis and host protective immunity, vaccine preparation and characteristics, stimulated host responses after vaccination and protection efficacy after challenge. Vaccine-related pathogen and host genes are also annotated and available for searching through customized BLAST programs. All VIOLIN data are available for download in an eXtensible Markup Language (XML)-based data exchange format. VIOLIN is expected to become a centralized source of vaccine information and to provide investigators in basic and clinical sciences with curated data and bioinformatics tools for vaccine research and development. VIOLIN is publicly available at http://www.violinet.org.},\\n bibtype = {article},\\n author = {Xiang, Zuoshuang and Todd, Thomas and Ku, Kim P and Kovacic, Bethany L and Larson, Charles B and Chen, Fang and Hodges, Andrew P and Tian, Yuying and Olenzek, Elizabeth A and Zhao, Boyang and Colby, Lesley A and Rush, Howard G and Gilsdorf, Janet R and Jourdian, George W and He, Yongqun},\\n doi = {10.1093/nar/gkm1039},\\n journal = {Nucleic Acids Research},\\n number = {Database}\\n}\",\"author_short\":[\"Xiang,  Z.\",\"Todd,  T.\",\"Ku,  K., P.\",\"Kovacic,  B., L.\",\"Larson,  C., B.\",\"Chen,  F.\",\"Hodges,  A., P.\",\"Tian,  Y.\",\"Olenzek,  E., A.\",\"Zhao,  B.\",\"Colby,  L., A.\",\"Rush,  H., G.\",\"Gilsdorf,  J., R.\",\"Jourdian,  G., W.\",\"He,  Y.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/37e90530-b184-24f3-7ccd-4f3793d6230c/2007-VIOLIN_vaccine_investigation_and_online_information_network.pdf.pdf\",\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/18025042,https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm1039\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"xiang-todd-ku-kovacic-larson-chen-hodges-tian-etal-violinvaccineinvestigationandonlineinformationnetwork-2007\",\"role\":\"author\",\"keyword\":[\"database\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":1,\"html\":\"\"},{\"title\":\"Kinetic mechanism for the excision of hypoxanthine by Escherichia coli AlkA and evidence for binding to DNA ends.\",\"type\":\"article\",\"year\":\"2011\",\"pages\":\"4350-9\",\"volume\":\"50\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/21491902,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3098123\",\"month\":\"5\",\"day\":\"24\",\"id\":\"2f72b967-3053-3dd8-924e-7d5f4f589512\",\"created\":\"2011-05-22T00:54:50.000Z\",\"accessed\":\"2011-04-16\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2021-03-28T17:21:31.527Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Zhao2011\",\"private_publication\":false,\"abstract\":\"The Escherichia coli 3-methyladenine DNA glycosylase II protein (AlkA) recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair pathway. Although the enzyme was one of the first DNA repair glycosylases to be discovered more than 25 years ago and there are multiple crystal structures, the mechanism is poorly understood. Therefore, we have characterized the kinetic mechanism for the AlkA-catalyzed excision of the deaminated purine, hypoxanthine. The multiple-turnover glycosylase assays are consistent with Michaelis-Menten kinetics. However, under single-turnover conditions that are commonly employed for studying other DNA glycosylases, we observe an unusual biphasic protein saturation curve. Initially, the observed rate constant for excision increases with an increasing level of AlkA protein, but at higher protein concentrations, the rate constant decreases. This behavior can be most easily explained by tight binding to DNA ends and by crowding of multiple AlkA protamers on the DNA. Consistent with this model, crystal structures have shown the preferential binding of AlkA to DNA ends. By varying the position of the lesion, we identified an asymmetric substrate that does not show inhibition at higher concentrations of AlkA, and we performed pre-steady state and steady state kinetic analysis. Unlike the situation in other glycosylases, release of the abasic product is faster than N-glycosidic bond cleavage. Nevertheless, AlkA exhibits significant product inhibition under multiple-turnover conditions, and it binds approximately 10-fold more tightly to an abasic site than to a hypoxanthine lesion site. This tight binding could help protect abasic sites when the adaptive response to DNA alkylation is activated and very high levels of AlkA protein are present.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and O'Brien, Patrick John\",\"doi\":\"10.1021/bi200232c\",\"journal\":\"Biochemistry\",\"number\":\"20\",\"bibtex\":\"@article{\\n title = {Kinetic mechanism for the excision of hypoxanthine by Escherichia coli AlkA and evidence for binding to DNA ends.},\\n type = {article},\\n year = {2011},\\n pages = {4350-9},\\n volume = {50},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/21491902,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3098123},\\n month = {5},\\n day = {24},\\n id = {2f72b967-3053-3dd8-924e-7d5f4f589512},\\n created = {2011-05-22T00:54:50.000Z},\\n accessed = {2011-04-16},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2021-03-28T17:21:31.527Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Zhao2011},\\n private_publication = {false},\\n abstract = {The Escherichia coli 3-methyladenine DNA glycosylase II protein (AlkA) recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair pathway. Although the enzyme was one of the first DNA repair glycosylases to be discovered more than 25 years ago and there are multiple crystal structures, the mechanism is poorly understood. Therefore, we have characterized the kinetic mechanism for the AlkA-catalyzed excision of the deaminated purine, hypoxanthine. The multiple-turnover glycosylase assays are consistent with Michaelis-Menten kinetics. However, under single-turnover conditions that are commonly employed for studying other DNA glycosylases, we observe an unusual biphasic protein saturation curve. Initially, the observed rate constant for excision increases with an increasing level of AlkA protein, but at higher protein concentrations, the rate constant decreases. This behavior can be most easily explained by tight binding to DNA ends and by crowding of multiple AlkA protamers on the DNA. Consistent with this model, crystal structures have shown the preferential binding of AlkA to DNA ends. By varying the position of the lesion, we identified an asymmetric substrate that does not show inhibition at higher concentrations of AlkA, and we performed pre-steady state and steady state kinetic analysis. Unlike the situation in other glycosylases, release of the abasic product is faster than N-glycosidic bond cleavage. Nevertheless, AlkA exhibits significant product inhibition under multiple-turnover conditions, and it binds approximately 10-fold more tightly to an abasic site than to a hypoxanthine lesion site. This tight binding could help protect abasic sites when the adaptive response to DNA alkylation is activated and very high levels of AlkA protein are present.},\\n bibtype = {article},\\n author = {Zhao, Boyang and O'Brien, Patrick John},\\n doi = {10.1021/bi200232c},\\n journal = {Biochemistry},\\n number = {20}\\n}\",\"author_short\":[\"Zhao,  B.\",\"O'Brien,  P., J.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7dc065ed-105f-7b57-7d5c-28b5328902e5/2011-Kinetic_mechanism_for_the_excision_of_hypoxanthine_by_Escherichia_coli_AlkA_and_evidence_for_binding_to_DNA_ends..pdf.pdf\",\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/21491902,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3098123\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-obrien-kineticmechanismfortheexcisionofhypoxanthinebyescherichiacolialkaandevidenceforbindingtodnaends-2011\",\"role\":\"author\",\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination.\",\"type\":\"article\",\"year\":\"2012\",\"pages\":\"C27-45\",\"volume\":\"302\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/21940666\",\"month\":\"1\",\"id\":\"7957de91-72c5-3dc3-a353-168f8c9396ea\",\"created\":\"2012-01-15T21:40:01.000Z\",\"accessed\":\"2012-01-10\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2017-03-25T18:28:36.677Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Zhao2012\",\"private_publication\":false,\"abstract\":\"Although extensive phosphoproteomic information is available for renal epithelial cells, previous emphasis has been on phosphorylation of serines and threonines with little focus on tyrosine phosphorylation. Here we have carried out large-scale identification of phosphotyrosine sites in pervanadate-treated native inner medullary collecting ducts of rat, with a view towards identification of physiological processes in epithelial cells that are potentially regulated by tyrosine phosphorylation. The method combined antibody-based affinity purification of tyrosine phosphorylated peptides coupled with immobilized metal ion chromatography to enrich tyrosine phosphopeptides, which were identified by LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins were identified. A large fraction of these sites have not been previously reported on standard phosphoproteomic databases. All results are accessible via an online database: http://helixweb.nih.gov/ESBL/Database/iPY/. Analysis of surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP, DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation. These motifs plus contextual information, integrated using the NetworKIN tool, suggest that the protein tyrosine kinases involved include members of the insulin- and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms and KEGG pathways whose protein elements are overrepresented in our data set point to structures involved in epithelial cell-cell and cell-matrix interactions (\\\"adherens junction,\\\" \\\"tight junction,\\\" and \\\"focal adhesion\\\") and to components of the actin cytoskeleton as major sites of tyrosine phosphorylation in these cells. In general, these findings mesh well with evidence that tyrosine phosphorylation plays a key role in epithelial polarity determination.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and Knepper, Mark A and Chou, Chung-Lin and Pisitkun, Trairak\",\"doi\":\"10.1152/ajpcell.00300.2011\",\"journal\":\"American journal of physiology. Cell physiology\",\"number\":\"1\",\"bibtex\":\"@article{\\n title = {Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination.},\\n type = {article},\\n year = {2012},\\n pages = {C27-45},\\n volume = {302},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/21940666},\\n month = {1},\\n id = {7957de91-72c5-3dc3-a353-168f8c9396ea},\\n created = {2012-01-15T21:40:01.000Z},\\n accessed = {2012-01-10},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2017-03-25T18:28:36.677Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Zhao2012},\\n private_publication = {false},\\n abstract = {Although extensive phosphoproteomic information is available for renal epithelial cells, previous emphasis has been on phosphorylation of serines and threonines with little focus on tyrosine phosphorylation. Here we have carried out large-scale identification of phosphotyrosine sites in pervanadate-treated native inner medullary collecting ducts of rat, with a view towards identification of physiological processes in epithelial cells that are potentially regulated by tyrosine phosphorylation. The method combined antibody-based affinity purification of tyrosine phosphorylated peptides coupled with immobilized metal ion chromatography to enrich tyrosine phosphopeptides, which were identified by LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins were identified. A large fraction of these sites have not been previously reported on standard phosphoproteomic databases. All results are accessible via an online database: http://helixweb.nih.gov/ESBL/Database/iPY/. Analysis of surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP, DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation. These motifs plus contextual information, integrated using the NetworKIN tool, suggest that the protein tyrosine kinases involved include members of the insulin- and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms and KEGG pathways whose protein elements are overrepresented in our data set point to structures involved in epithelial cell-cell and cell-matrix interactions (\\\"adherens junction,\\\" \\\"tight junction,\\\" and \\\"focal adhesion\\\") and to components of the actin cytoskeleton as major sites of tyrosine phosphorylation in these cells. In general, these findings mesh well with evidence that tyrosine phosphorylation plays a key role in epithelial polarity determination.},\\n bibtype = {article},\\n author = {Zhao, Boyang and Knepper, Mark A and Chou, Chung-Lin and Pisitkun, Trairak},\\n doi = {10.1152/ajpcell.00300.2011},\\n journal = {American journal of physiology. Cell physiology},\\n number = {1}\\n}\",\"author_short\":[\"Zhao,  B.\",\"Knepper,  M., A.\",\"Chou,  C.\",\"Pisitkun,  T.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6ee512db-5429-ca21-25a7-43b3840f2dc3/2012-Large-scale_phosphotyrosine_proteomic_profiling_of_rat_renal_collecting_duct_epithelium_reveals_predominance_of_pro.pdf.pdf\",\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/21940666\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-knepper-chou-pisitkun-largescalephosphotyrosineproteomicprofilingofratrenalcollectingductepitheliumrevealspredominanceofproteinsinvolvedincellpolaritydetermination-2012\",\"role\":\"author\",\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"CPhos: A program to calculate and visualize evolutionarily conserved functional phosphorylation sites.\",\"type\":\"article\",\"year\":\"2012\",\"keywords\":\"bioinformatics,conservation,functional significance,information theory,phos-\",\"pages\":\"3299-303\",\"volume\":\"12\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/23001821\",\"month\":\"11\",\"day\":\"24\",\"id\":\"c67c6412-4c88-3f86-b148-2518ab2bea53\",\"created\":\"2012-11-29T12:49:09.000Z\",\"accessed\":\"2012-11-29\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2017-03-25T18:28:36.677Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Zhao2012a\",\"private_publication\":false,\"abstract\":\"Profiling using high-throughput MS has discovered an overwhelming number of novel protein phosphorylation sites (\\\"phosphosites\\\"). However, the functional relevance of these sites is not always clear. In light of recent studies on the evolutionary mechanism of phosphorylation, we have developed CPhos, a Java program that can assess the conservation of phosphosites among species using an information theory-based approach. The degree of conservation established using CPhos can be used to assess the functional significance of phosphosites. CPhos has a user friendly graphical user interface and is available both as a web service and as a standalone Java application to assist phosphoproteomic researchers in analyzing and prioritizing lists of phosphosites for further experimental validation. CPhos can be accessed or downloaded at http://helixweb.nih.gov/CPhos/.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and Pisitkun, Trairak and Hoffert, Jason D and Knepper, Mark a and Saeed, Fahad\",\"doi\":\"10.1002/pmic.201200189\",\"journal\":\"Proteomics\",\"number\":\"22\",\"bibtex\":\"@article{\\n title = {CPhos: A program to calculate and visualize evolutionarily conserved functional phosphorylation sites.},\\n type = {article},\\n year = {2012},\\n keywords = {bioinformatics,conservation,functional significance,information theory,phos-},\\n pages = {3299-303},\\n volume = {12},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/23001821},\\n month = {11},\\n day = {24},\\n id = {c67c6412-4c88-3f86-b148-2518ab2bea53},\\n created = {2012-11-29T12:49:09.000Z},\\n accessed = {2012-11-29},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2017-03-25T18:28:36.677Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Zhao2012a},\\n private_publication = {false},\\n abstract = {Profiling using high-throughput MS has discovered an overwhelming number of novel protein phosphorylation sites (\\\"phosphosites\\\"). However, the functional relevance of these sites is not always clear. In light of recent studies on the evolutionary mechanism of phosphorylation, we have developed CPhos, a Java program that can assess the conservation of phosphosites among species using an information theory-based approach. The degree of conservation established using CPhos can be used to assess the functional significance of phosphosites. CPhos has a user friendly graphical user interface and is available both as a web service and as a standalone Java application to assist phosphoproteomic researchers in analyzing and prioritizing lists of phosphosites for further experimental validation. CPhos can be accessed or downloaded at http://helixweb.nih.gov/CPhos/.},\\n bibtype = {article},\\n author = {Zhao, Boyang and Pisitkun, Trairak and Hoffert, Jason D and Knepper, Mark a and Saeed, Fahad},\\n doi = {10.1002/pmic.201200189},\\n journal = {Proteomics},\\n number = {22}\\n}\",\"author_short\":[\"Zhao,  B.\",\"Pisitkun,  T.\",\"Hoffert,  J., D.\",\"Knepper,  M., a.\",\"Saeed,  F.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/11ae6f52-c251-69bb-04fd-820fdc30a339/2012-CPhos_A_program_to_calculate_and_visualize_evolutionarily_conserved_functional_phosphorylation_sites..pdf.pdf\",\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/23001821\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-pisitkun-hoffert-knepper-saeed-cphosaprogramtocalculateandvisualizeevolutionarilyconservedfunctionalphosphorylationsites-2012\",\"role\":\"author\",\"keyword\":[\"bioinformatics\",\"conservation\",\"functional significance\",\"information theory\",\"phos-\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule.\",\"type\":\"article\",\"year\":\"2011\",\"keywords\":\"Amino Acid Sequence,Animals,Chromatography,Distal,Distal: chemistry,Distal: cytology,Humans,Kidney Tubules,Liquid,Male,Membrane Proteins,Membrane Proteins: analysis,Membrane Proteins: genetics,Molecular Sequence Data,Phosphopeptides,Phosphopeptides: analysis,Phosphopeptides: genetics,Phosphoproteins,Phosphoproteins: analysis,Phosphoproteins: genetics,Protein Conformation,Protein Structure,Proteome,Proteome: analysis,Proximal,Proximal: chemistry,Proximal: cytology,Rats,Sequence Alignment,Sprague-Dawley,Tandem Mass Spectrometry,Tertiary\",\"pages\":\"C755-70\",\"volume\":\"300\",\"websites\":\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3074622&tool=pmcentrez&rendertype=abstract\",\"month\":\"4\",\"id\":\"1473c45e-b556-3709-bde0-a19c51ec07ca\",\"created\":\"2013-01-28T03:01:54.000Z\",\"accessed\":\"2013-01-27\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2017-03-25T18:28:36.677Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Feric2011\",\"private_publication\":false,\"abstract\":\"Recent advances in mass spectrometry (MS) have provided means for large-scale phosphoproteomic profiling of specific tissues. Here, we report results from large-scale tandem MS [liquid chromatography (LC)-MS/MS]-based phosphoproteomic profiling of biochemically isolated membranes from the renal cortex, with focus on transporters and regulatory proteins. Data sets were filtered (by target-decoy analysis) to limit false-positive identifications to <2%. A total of 7,125 unique nonphosphorylated and 743 unique phosphorylated peptides were identified. Among the phosphopeptides identified were sites on transporter proteins, i.e., solute carrier (Slc, n = 63), ATP-binding cassette (Abc, n = 4), and aquaporin (Aqp, n = 3) family proteins. Database searches reveal that a majority of the phosphorylation sites identified in transporter proteins were previously unreported. Most of the Slc family proteins are apical or basolateral transporters expressed in proximal tubule cells, including proteins known to mediate transport of glucose, amino acids, organic ions, and inorganic ions. In addition, we identified potentially important phosphorylation sites for transport proteins from distal nephron segments, including the bumetanide-sensitive Na-K-2Cl cotransporter (Slc12a1 or NKCC2) at Ser(87), Thr(101), and Ser(126) and the thiazide-sensitive Na-Cl cotransporter (Slc12a3 or NCC) at Ser(71) and Ser(124). A subset of phosphorylation sites in regulatory proteins coincided with known functional motifs, suggesting specific regulatory roles. An online database from this study (http://dir.nhlbi.nih.gov/papers/lkem/rcmpd/) provides a resource for future studies of transporter regulation.\",\"bibtype\":\"article\",\"author\":\"Feric, Marina and Zhao, Boyang and Hoffert, Jason D and Pisitkun, Trairak and Knepper, Mark A\",\"doi\":\"10.1152/ajpcell.00360.2010\",\"journal\":\"American journal of physiology. Cell physiology\",\"number\":\"4\",\"bibtex\":\"@article{\\n title = {Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule.},\\n type = {article},\\n year = {2011},\\n keywords = {Amino Acid Sequence,Animals,Chromatography,Distal,Distal: chemistry,Distal: cytology,Humans,Kidney Tubules,Liquid,Male,Membrane Proteins,Membrane Proteins: analysis,Membrane Proteins: genetics,Molecular Sequence Data,Phosphopeptides,Phosphopeptides: analysis,Phosphopeptides: genetics,Phosphoproteins,Phosphoproteins: analysis,Phosphoproteins: genetics,Protein Conformation,Protein Structure,Proteome,Proteome: analysis,Proximal,Proximal: chemistry,Proximal: cytology,Rats,Sequence Alignment,Sprague-Dawley,Tandem Mass Spectrometry,Tertiary},\\n pages = {C755-70},\\n volume = {300},\\n websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3074622&tool=pmcentrez&rendertype=abstract},\\n month = {4},\\n id = {1473c45e-b556-3709-bde0-a19c51ec07ca},\\n created = {2013-01-28T03:01:54.000Z},\\n accessed = {2013-01-27},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2017-03-25T18:28:36.677Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Feric2011},\\n private_publication = {false},\\n abstract = {Recent advances in mass spectrometry (MS) have provided means for large-scale phosphoproteomic profiling of specific tissues. Here, we report results from large-scale tandem MS [liquid chromatography (LC)-MS/MS]-based phosphoproteomic profiling of biochemically isolated membranes from the renal cortex, with focus on transporters and regulatory proteins. Data sets were filtered (by target-decoy analysis) to limit false-positive identifications to <2%. A total of 7,125 unique nonphosphorylated and 743 unique phosphorylated peptides were identified. Among the phosphopeptides identified were sites on transporter proteins, i.e., solute carrier (Slc, n = 63), ATP-binding cassette (Abc, n = 4), and aquaporin (Aqp, n = 3) family proteins. Database searches reveal that a majority of the phosphorylation sites identified in transporter proteins were previously unreported. Most of the Slc family proteins are apical or basolateral transporters expressed in proximal tubule cells, including proteins known to mediate transport of glucose, amino acids, organic ions, and inorganic ions. In addition, we identified potentially important phosphorylation sites for transport proteins from distal nephron segments, including the bumetanide-sensitive Na-K-2Cl cotransporter (Slc12a1 or NKCC2) at Ser(87), Thr(101), and Ser(126) and the thiazide-sensitive Na-Cl cotransporter (Slc12a3 or NCC) at Ser(71) and Ser(124). A subset of phosphorylation sites in regulatory proteins coincided with known functional motifs, suggesting specific regulatory roles. An online database from this study (http://dir.nhlbi.nih.gov/papers/lkem/rcmpd/) provides a resource for future studies of transporter regulation.},\\n bibtype = {article},\\n author = {Feric, Marina and Zhao, Boyang and Hoffert, Jason D and Pisitkun, Trairak and Knepper, Mark A},\\n doi = {10.1152/ajpcell.00360.2010},\\n journal = {American journal of physiology. Cell physiology},\\n number = {4}\\n}\",\"author_short\":[\"Feric,  M.\",\"Zhao,  B.\",\"Hoffert,  J., D.\",\"Pisitkun,  T.\",\"Knepper,  M., A.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/47a0f115-d9a1-5609-3972-d12e9f347879/2011-Large-scale_phosphoproteomic_analysis_of_membrane_proteins_in_renal_proximal_and_distal_tubule..pdf.pdf\",\"Website\":\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3074622&tool=pmcentrez&rendertype=abstract\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"feric-zhao-hoffert-pisitkun-knepper-largescalephosphoproteomicanalysisofmembraneproteinsinrenalproximalanddistaltubule-2011\",\"role\":\"author\",\"keyword\":[\"Amino Acid Sequence\",\"Animals\",\"Chromatography\",\"Distal\",\"Distal: chemistry\",\"Distal: cytology\",\"Humans\",\"Kidney Tubules\",\"Liquid\",\"Male\",\"Membrane Proteins\",\"Membrane Proteins: analysis\",\"Membrane Proteins: genetics\",\"Molecular Sequence Data\",\"Phosphopeptides\",\"Phosphopeptides: analysis\",\"Phosphopeptides: genetics\",\"Phosphoproteins\",\"Phosphoproteins: analysis\",\"Phosphoproteins: genetics\",\"Protein Conformation\",\"Protein Structure\",\"Proteome\",\"Proteome: analysis\",\"Proximal\",\"Proximal: chemistry\",\"Proximal: cytology\",\"Rats\",\"Sequence Alignment\",\"Sprague-Dawley\",\"Tandem Mass Spectrometry\",\"Tertiary\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Updates on the web-based VIOLIN vaccine database and analysis system.\",\"type\":\"article\",\"year\":\"2014\",\"pages\":\"D1124-32\",\"volume\":\"42\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/24259431\",\"month\":\"1\",\"day\":\"1\",\"id\":\"03a23edb-5633-3c44-af14-a2e41fed35f1\",\"created\":\"2014-03-06T08:30:02.000Z\",\"accessed\":\"2014-01-22\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2017-03-25T18:28:36.677Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"He2014\",\"private_publication\":false,\"abstract\":\"The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.\",\"bibtype\":\"article\",\"author\":\"He, Yongqun and Racz, Rebecca and Sayers, Samantha and Lin, Yu and Todd, Thomas and Hur, Junguk and Li, Xinna and Patel, Mukti and Zhao, Boyang and Chung, Monica and Ostrow, Joseph and Sylora, Andrew and Dungarani, Priya and Ulysse, Guerlain and Kochhar, Kanika and Vidri, Boris and Strait, Kelsey and Jourdian, George W and Xiang, Zuoshuang\",\"doi\":\"10.1093/nar/gkt1133\",\"journal\":\"Nucleic acids research\",\"number\":\"1\",\"bibtex\":\"@article{\\n title = {Updates on the web-based VIOLIN vaccine database and analysis system.},\\n type = {article},\\n year = {2014},\\n pages = {D1124-32},\\n volume = {42},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/24259431},\\n month = {1},\\n day = {1},\\n id = {03a23edb-5633-3c44-af14-a2e41fed35f1},\\n created = {2014-03-06T08:30:02.000Z},\\n accessed = {2014-01-22},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2017-03-25T18:28:36.677Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {He2014},\\n private_publication = {false},\\n abstract = {The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.},\\n bibtype = {article},\\n author = {He, Yongqun and Racz, Rebecca and Sayers, Samantha and Lin, Yu and Todd, Thomas and Hur, Junguk and Li, Xinna and Patel, Mukti and Zhao, Boyang and Chung, Monica and Ostrow, Joseph and Sylora, Andrew and Dungarani, Priya and Ulysse, Guerlain and Kochhar, Kanika and Vidri, Boris and Strait, Kelsey and Jourdian, George W and Xiang, Zuoshuang},\\n doi = {10.1093/nar/gkt1133},\\n journal = {Nucleic acids research},\\n number = {1}\\n}\",\"author_short\":[\"He,  Y.\",\"Racz,  R.\",\"Sayers,  S.\",\"Lin,  Y.\",\"Todd,  T.\",\"Hur,  J.\",\"Li,  X.\",\"Patel,  M.\",\"Zhao,  B.\",\"Chung,  M.\",\"Ostrow,  J.\",\"Sylora,  A.\",\"Dungarani,  P.\",\"Ulysse,  G.\",\"Kochhar,  K.\",\"Vidri,  B.\",\"Strait,  K.\",\"Jourdian,  G., W.\",\"Xiang,  Z.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6b25c1e8-a4f7-8e1b-529e-7c227d53d087/2014-Updates_on_the_web-based_VIOLIN_vaccine_database_and_analysis_system..pdf.pdf\",\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/24259431\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"he-racz-sayers-lin-todd-hur-li-patel-etal-updatesonthewebbasedviolinvaccinedatabaseandanalysissystem-2014\",\"role\":\"author\",\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Intratumor heterogeneity alters most effective drugs in designed combinations.\",\"type\":\"article\",\"year\":\"2014\",\"pages\":\"10773-8\",\"volume\":\"111\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/25002493,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4115561&tool=pmcentrez&rendertype=abstract\",\"month\":\"7\",\"day\":\"22\",\"id\":\"8eaa7f79-33fa-32db-b9fe-cd246ddc3e3b\",\"created\":\"2014-08-03T05:54:23.000Z\",\"accessed\":\"2014-08-18\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2017-03-25T18:28:36.677Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Zhao2014\",\"folder_uuids\":\"7e96e842-b029-41e6-a73f-7511890cd62e\",\"private_publication\":false,\"abstract\":\"The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and Hemann, Michael T and Lauffenburger, Douglas A\",\"doi\":\"10.1073/pnas.1323934111\",\"journal\":\"Proceedings of the National Academy of Sciences of the United States of America\",\"number\":\"29\",\"keywords\":\"drug combination,drug optimization\",\"bibtex\":\"@article{\\n title = {Intratumor heterogeneity alters most effective drugs in designed combinations.},\\n type = {article},\\n year = {2014},\\n pages = {10773-8},\\n volume = {111},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/25002493,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4115561&tool=pmcentrez&rendertype=abstract},\\n month = {7},\\n day = {22},\\n id = {8eaa7f79-33fa-32db-b9fe-cd246ddc3e3b},\\n created = {2014-08-03T05:54:23.000Z},\\n accessed = {2014-08-18},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2017-03-25T18:28:36.677Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Zhao2014},\\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\\n private_publication = {false},\\n abstract = {The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.},\\n bibtype = {article},\\n author = {Zhao, Boyang and Hemann, Michael T and Lauffenburger, Douglas A},\\n doi = {10.1073/pnas.1323934111},\\n journal = {Proceedings of the National Academy of Sciences of the United States of America},\\n number = {29},\\n keywords = {drug combination,drug optimization}\\n}\",\"author_short\":[\"Zhao,  B.\",\"Hemann,  M., T.\",\"Lauffenburger,  D., A.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7860a1ef-e4b6-9a47-4f4f-7088d41d8973/2014-Intratumor_heterogeneity_alters_most_effective_drugs_in_designed_combinations..pdf.pdf\",\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/25002493,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4115561&tool=pmcentrez&rendertype=abstract\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-hemann-lauffenburger-intratumorheterogeneityaltersmosteffectivedrugsindesignedcombinations-2014\",\"role\":\"author\",\"keyword\":[\"drug combination\",\"drug optimization\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors\",\"type\":\"article\",\"year\":\"2015\",\"keywords\":\"2015,2015 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and Rivera, Victor M and Garner, Andrew and Gonzalvez, Francois},\\n doi = {10.18632/oncotarget.5066},\\n journal = {Oncotarget},\\n number = {32}\\n}\",\"author_short\":[\"Baker,  T.\",\"Nerle,  S.\",\"Pritchard,  J.\",\"Zhao,  B.\",\"Rivera,  V., M.\",\"Garner,  A.\",\"Gonzalvez,  F.\"],\"urls\":{\"Website\":\"http://www.oncotarget.com/abstract/5066\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"baker-nerle-pritchard-zhao-rivera-garner-gonzalvez-acquisitionofasingleezh2d1domainmutationconfersacquiredresistancetoezh2targetedinhibitors-2015\",\"role\":\"author\",\"keyword\":[\"2015\",\"2015 accepted\",\"august 20\",\"cancer\",\"drug resistance\",\"epigenetics\",\"equally to this work\",\"ezh2\",\"july 17\",\"mutation\",\"published\",\"received\",\"september 02\",\"these authors have contributed\"],\"metadata\":{\"authorlinks\":{\"zhao,  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J., R.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/66c7ef86-6636-e71d-072f-4a6c778f88a9/2016-Inherited_Disease_Genetics_Improves_the_Identification_of_Cancer-Associated_Genes.pdf.pdf\",\"Website\":\"http://dx.plos.org/10.1371/journal.pgen.1006081\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-pritchard-inheriteddiseasegeneticsimprovestheidentificationofcancerassociatedgenes-2016\",\"role\":\"author\",\"keyword\":[\"cancer driver identification\",\"systems biology\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations\",\"type\":\"article\",\"year\":\"2016\",\"pages\":\"36198\",\"volume\":\"6\",\"websites\":\"http://www.nature.com/articles/srep36198\",\"publisher\":\"Nature Publishing Group\",\"id\":\"10a79cac-8cf7-3d76-89f4-87f2a064a0cf\",\"created\":\"2016-11-08T05:25:01.000Z\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2020-03-31T13:50:24.548Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Sun2016\",\"folder_uuids\":\"7e96e842-b029-41e6-a73f-7511890cd62e\",\"private_publication\":false,\"bibtype\":\"article\",\"author\":\"Sun, Daphne and Dalin, Simona and Hemann, Michael T. and Lauffenburger, Douglas A. and Zhao, Boyang\",\"doi\":\"10.1038/srep36198\",\"journal\":\"Scientific Reports\",\"number\":\"October\",\"keywords\":\"drug combination,drug resistance\",\"bibtex\":\"@article{\\n title = {Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations},\\n type = {article},\\n year = {2016},\\n pages = {36198},\\n volume = {6},\\n websites = {http://www.nature.com/articles/srep36198},\\n publisher = {Nature Publishing Group},\\n id = {10a79cac-8cf7-3d76-89f4-87f2a064a0cf},\\n created = {2016-11-08T05:25:01.000Z},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2020-03-31T13:50:24.548Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Sun2016},\\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\\n private_publication = {false},\\n bibtype = {article},\\n author = {Sun, Daphne and Dalin, Simona and Hemann, Michael T. and Lauffenburger, Douglas A. and Zhao, Boyang},\\n doi = {10.1038/srep36198},\\n journal = {Scientific Reports},\\n number = {October},\\n keywords = {drug combination,drug resistance}\\n}\",\"author_short\":[\"Sun,  D.\",\"Dalin,  S.\",\"Hemann,  M., T.\",\"Lauffenburger,  D., A.\",\"Zhao,  B.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/01953cb5-363c-6413-436a-9c6e5dd32945/Sun_2016_Sci_Rep___differential_selective_pressure_alter_drug_resistance_rate.pdf.pdf\",\"Website\":\"http://www.nature.com/articles/srep36198\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"sun-dalin-hemann-lauffenburger-zhao-differentialselectivepressurealtersrateofdrugresistanceacquisitioninheterogeneoustumorpopulations-2016\",\"role\":\"author\",\"keyword\":[\"drug combination\",\"drug resistance\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Modeling Tumor Clonal Evolution for Drug Combinations Design\",\"type\":\"article\",\"year\":\"2016\",\"keywords\":\"clonal evolution,drug combination,drug optimization,drug resistance,drug scheduling,mathematical modeling,mathematical programming,review,tumor heterogeneity\",\"pages\":\"144-158\",\"volume\":\"2\",\"websites\":\"http://linkinghub.elsevier.com/retrieve/pii/S2405803316000212\",\"month\":\"3\",\"publisher\":\"Elsevier Inc.\",\"id\":\"605cd43c-a5e1-3fb2-92bb-c19d2f0430b0\",\"created\":\"2017-04-12T01:29:39.680Z\",\"file_attached\":\"true\",\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2017-10-27T16:11:01.757Z\",\"read\":false,\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Zhao2016b\",\"folder_uuids\":\"7e96e842-b029-41e6-a73f-7511890cd62e\",\"private_publication\":false,\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and Hemann, Michael T. and Lauffenburger, Douglas A.\",\"doi\":\"10.1016/j.trecan.2016.02.001\",\"journal\":\"Trends in Cancer\",\"number\":\"3\",\"bibtex\":\"@article{\\n title = {Modeling Tumor Clonal Evolution for Drug Combinations Design},\\n type = {article},\\n year = {2016},\\n keywords = {clonal evolution,drug combination,drug optimization,drug resistance,drug scheduling,mathematical modeling,mathematical programming,review,tumor heterogeneity},\\n pages = {144-158},\\n volume = {2},\\n websites = {http://linkinghub.elsevier.com/retrieve/pii/S2405803316000212},\\n month = {3},\\n publisher = {Elsevier Inc.},\\n id = {605cd43c-a5e1-3fb2-92bb-c19d2f0430b0},\\n created = {2017-04-12T01:29:39.680Z},\\n file_attached = {true},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2017-10-27T16:11:01.757Z},\\n read = {false},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Zhao2016b},\\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\\n private_publication = {false},\\n bibtype = {article},\\n author = {Zhao, Boyang and Hemann, Michael T. and Lauffenburger, Douglas A.},\\n doi = {10.1016/j.trecan.2016.02.001},\\n journal = {Trends in Cancer},\\n number = {3}\\n}\",\"author_short\":[\"Zhao,  B.\",\"Hemann,  M., T.\",\"Lauffenburger,  D., A.\"],\"urls\":{\"Paper\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/429fb4d5-10e7-57a5-5565-934956e4743c/Zhao_2016_Trends_Cancer___review_modeling_tumor_clonal_evolution_for_drug_combinations.pdf.pdf\",\"Website\":\"http://linkinghub.elsevier.com/retrieve/pii/S2405803316000212\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-hemann-lauffenburger-modelingtumorclonalevolutionfordrugcombinationsdesign-2016\",\"role\":\"author\",\"keyword\":[\"clonal evolution\",\"drug combination\",\"drug optimization\",\"drug resistance\",\"drug scheduling\",\"mathematical modeling\",\"mathematical programming\",\"review\",\"tumor heterogeneity\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Clinical Data Extraction and Normalization of Cyrillic Electronic Health Records Via Deep-Learning Natural Language Processing.\",\"type\":\"article\",\"year\":\"2019\",\"pages\":\"1-9\",\"volume\":\"3\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/31577448\",\"month\":\"9\",\"id\":\"59dcce28-2d06-3c9b-bcf0-3effa4d08552\",\"created\":\"2019-10-05T17:49:58.220Z\",\"file_attached\":false,\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2019-11-07T19:06:38.483Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"folder_uuids\":\"7e96e842-b029-41e6-a73f-7511890cd62e\",\"private_publication\":false,\"abstract\":\"PURPOSE A substantial portion of medical data is unstructured. Extracting data from unstructured text presents a barrier to advancing clinical research and improving patient care. In addition, ongoing studies have been focused predominately on the English language, whereas inflected languages with non-Latin alphabets (such as Slavic languages with a Cyrillic alphabet) present numerous linguistic challenges. We developed deep-learning-based natural language processing algorithms for automatically extracting biomarker status of patients with breast cancer from three oncology centers in Bulgaria. METHODS We used dual embeddings for English and Bulgarian languages, encoding both syntactic and polarity information for the words. The embeddings were subsequently aligned so that they were in the same vector space. The embeddings were used as input to convolutional or recurrent neural networks to derive the biomarker status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. RESULTS We showed that we can resolve ambiguity in highly variable medical text containing both Latin and Cyrillic text. Final models incorporating both English and Bulgarian syntax and polarity embeddings achieved F1 scores of 0.90 or higher for all estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 biomarkers. The models were robust against human errors originally found in the training set. In addition, such models can be extended for analyzing text containing words not seen during training. CONCLUSION By using several techniques that incorporate dual-word embeddings encoding syntactic and polarity information in two languages followed by deep neural network architectures, we show that researchers can extract and normalize parameters within medical data. The principles described here can be used to analyze Cyrillic or Latin mixed medical text and extract other parameters.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang\",\"doi\":\"10.1200/CCI.19.00057\",\"journal\":\"JCO clinical cancer informatics\",\"number\":\"2\",\"bibtex\":\"@article{\\n title = {Clinical Data Extraction and Normalization of Cyrillic Electronic Health Records Via Deep-Learning Natural Language Processing.},\\n type = {article},\\n year = {2019},\\n pages = {1-9},\\n volume = {3},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/31577448},\\n month = {9},\\n id = {59dcce28-2d06-3c9b-bcf0-3effa4d08552},\\n created = {2019-10-05T17:49:58.220Z},\\n file_attached = {false},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2019-11-07T19:06:38.483Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\\n private_publication = {false},\\n abstract = {PURPOSE A substantial portion of medical data is unstructured. Extracting data from unstructured text presents a barrier to advancing clinical research and improving patient care. In addition, ongoing studies have been focused predominately on the English language, whereas inflected languages with non-Latin alphabets (such as Slavic languages with a Cyrillic alphabet) present numerous linguistic challenges. We developed deep-learning-based natural language processing algorithms for automatically extracting biomarker status of patients with breast cancer from three oncology centers in Bulgaria. METHODS We used dual embeddings for English and Bulgarian languages, encoding both syntactic and polarity information for the words. The embeddings were subsequently aligned so that they were in the same vector space. The embeddings were used as input to convolutional or recurrent neural networks to derive the biomarker status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. RESULTS We showed that we can resolve ambiguity in highly variable medical text containing both Latin and Cyrillic text. Final models incorporating both English and Bulgarian syntax and polarity embeddings achieved F1 scores of 0.90 or higher for all estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 biomarkers. The models were robust against human errors originally found in the training set. In addition, such models can be extended for analyzing text containing words not seen during training. CONCLUSION By using several techniques that incorporate dual-word embeddings encoding syntactic and polarity information in two languages followed by deep neural network architectures, we show that researchers can extract and normalize parameters within medical data. The principles described here can be used to analyze Cyrillic or Latin mixed medical text and extract other parameters.},\\n bibtype = {article},\\n author = {Zhao, Boyang},\\n doi = {10.1200/CCI.19.00057},\\n journal = {JCO clinical cancer informatics},\\n number = {2}\\n}\",\"author_short\":[\"Zhao,  B.\"],\"urls\":{\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/31577448\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-clinicaldataextractionandnormalizationofcyrillicelectronichealthrecordsviadeeplearningnaturallanguageprocessing-2019\",\"role\":\"author\",\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":1,\"html\":\"\"},{\"title\":\"Evolution of the nonsense-mediated decay pathway is associated with decreased cytolytic immune infiltration.\",\"type\":\"article\",\"year\":\"2019\",\"pages\":\"e1007467\",\"volume\":\"15\",\"websites\":\"http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270\",\"month\":\"10\",\"day\":\"28\",\"id\":\"e4a1b363-f728-326d-973a-7e1cb778472c\",\"created\":\"2019-11-07T19:06:38.129Z\",\"file_attached\":false,\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2021-01-16T10:42:35.980Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"private_publication\":false,\"abstract\":\"The somatic co-evolution of tumors and the cellular immune responses that combat them drives the diversity of immune-tumor interactions. This includes tumor mutations that generate neo-antigenic epitopes that elicit cytotoxic T-cell activity and subsequent pressure to select for genetic loss of antigen presentation. Most studies have focused on how tumor missense mutations can drive tumor immunity, but frameshift mutations have the potential to create far greater antigenic diversity. However, expression of this antigenic diversity is potentially regulated by Nonsense Mediated Decay (NMD) and NMD has been shown to be of variable efficiency in cancers. Here we studied how mutational changes influence global NMD and cytolytic immune responses. Using TCGA datasets, we derived novel patient-level metrics of 'NMD burden' and interrogated how different mutation and most importantly NMD burdens influence cytolytic activity using machine learning models and survival outcomes. We find that NMD is a significant and independent predictor of immune cytolytic activity. Different indications exhibited varying dependence on NMD and mutation burden features. We also observed significant co-alteration of genes in the NMD pathway, with a global increase in NMD efficiency in patients with NMD co-alterations. Finally, NMD burden also stratified patient survival in multivariate regression models in subset of cancer types. Our work suggests that beyond selecting for mutations that elicit NMD in tumor suppressors, tumor evolution may react to the selective pressure generated by inflammation to globally enhance NMD through coordinated amplification and/or mutation.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and Pritchard, Justin R\",\"doi\":\"10.1371/journal.pcbi.1007467\",\"journal\":\"PLoS computational biology\",\"number\":\"10\",\"bibtex\":\"@article{\\n title = {Evolution of the nonsense-mediated decay pathway is associated with decreased cytolytic immune infiltration.},\\n type = {article},\\n year = {2019},\\n pages = {e1007467},\\n volume = {15},\\n websites = {http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270},\\n month = {10},\\n day = {28},\\n id = {e4a1b363-f728-326d-973a-7e1cb778472c},\\n created = {2019-11-07T19:06:38.129Z},\\n file_attached = {false},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2021-01-16T10:42:35.980Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n private_publication = {false},\\n abstract = {The somatic co-evolution of tumors and the cellular immune responses that combat them drives the diversity of immune-tumor interactions. This includes tumor mutations that generate neo-antigenic epitopes that elicit cytotoxic T-cell activity and subsequent pressure to select for genetic loss of antigen presentation. Most studies have focused on how tumor missense mutations can drive tumor immunity, but frameshift mutations have the potential to create far greater antigenic diversity. However, expression of this antigenic diversity is potentially regulated by Nonsense Mediated Decay (NMD) and NMD has been shown to be of variable efficiency in cancers. Here we studied how mutational changes influence global NMD and cytolytic immune responses. Using TCGA datasets, we derived novel patient-level metrics of 'NMD burden' and interrogated how different mutation and most importantly NMD burdens influence cytolytic activity using machine learning models and survival outcomes. We find that NMD is a significant and independent predictor of immune cytolytic activity. Different indications exhibited varying dependence on NMD and mutation burden features. We also observed significant co-alteration of genes in the NMD pathway, with a global increase in NMD efficiency in patients with NMD co-alterations. Finally, NMD burden also stratified patient survival in multivariate regression models in subset of cancer types. Our work suggests that beyond selecting for mutations that elicit NMD in tumor suppressors, tumor evolution may react to the selective pressure generated by inflammation to globally enhance NMD through coordinated amplification and/or mutation.},\\n bibtype = {article},\\n author = {Zhao, Boyang and Pritchard, Justin R},\\n doi = {10.1371/journal.pcbi.1007467},\\n journal = {PLoS computational biology},\\n number = {10}\\n}\",\"author_short\":[\"Zhao,  B.\",\"Pritchard,  J., R.\"],\"urls\":{\"Website\":\"http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-pritchard-evolutionofthenonsensemediateddecaypathwayisassociatedwithdecreasedcytolyticimmuneinfiltration-2019\",\"role\":\"author\",\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":1,\"html\":\"\"},{\"title\":\"Multi-scale Predictions of Drug Resistance Epidemiology Identify Design Principles for Rational Drug Design\",\"type\":\"article\",\"year\":\"2020\",\"pages\":\"3951-3963.e4\",\"volume\":\"30\",\"websites\":\"https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898\",\"month\":\"3\",\"publisher\":\"ElsevierCompany.\",\"id\":\"0269e27f-97b5-32f9-a162-754072105b5d\",\"created\":\"2020-03-24T21:54:22.483Z\",\"file_attached\":false,\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2020-11-01T16:27:27.894Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"private_publication\":false,\"bibtype\":\"article\",\"author\":\"Leighow, Scott M and Liu, Chuan and Inam, Haider and Zhao, Boyang and Pritchard, Justin R\",\"doi\":\"10.1016/j.celrep.2020.02.108\",\"journal\":\"Cell Reports\",\"number\":\"12\",\"bibtex\":\"@article{\\n title = {Multi-scale Predictions of Drug Resistance Epidemiology Identify Design Principles for Rational Drug Design},\\n type = {article},\\n year = {2020},\\n pages = {3951-3963.e4},\\n volume = {30},\\n websites = {https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898},\\n month = {3},\\n publisher = {ElsevierCompany.},\\n id = {0269e27f-97b5-32f9-a162-754072105b5d},\\n created = {2020-03-24T21:54:22.483Z},\\n file_attached = {false},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2020-11-01T16:27:27.894Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n private_publication = {false},\\n bibtype = {article},\\n author = {Leighow, Scott M and Liu, Chuan and Inam, Haider and Zhao, Boyang and Pritchard, Justin R},\\n doi = {10.1016/j.celrep.2020.02.108},\\n journal = {Cell Reports},\\n number = {12}\\n}\",\"author_short\":[\"Leighow,  S., M.\",\"Liu,  C.\",\"Inam,  H.\",\"Zhao,  B.\",\"Pritchard,  J., R.\"],\"urls\":{\"Website\":\"https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"leighow-liu-inam-zhao-pritchard-multiscalepredictionsofdrugresistanceepidemiologyidentifydesignprinciplesforrationaldrugdesign-2020\",\"role\":\"author\",\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Semantic search with domain-specific word-embedding and production monitoring in Fintech\",\"type\":\"inproceedings\",\"year\":\"2020\",\"pages\":\"28-33\",\"id\":\"90ca5cbd-dfdb-3fdc-8ef5-eccd9286f6b9\",\"created\":\"2020-12-07T09:11:03.324Z\",\"file_attached\":false,\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2020-12-12T17:34:11.539Z\",\"read\":false,\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"folder_uuids\":\"7e96e842-b029-41e6-a73f-7511890cd62e\",\"private_publication\":false,\"bibtype\":\"inproceedings\",\"author\":\"Farmanbar, Mojtaba and Ommeren, Nikki Van and Zhao, Boyang\",\"booktitle\":\"Proceedings of the 28th International Conference on Computational Linguistics: System Demonstrations\",\"bibtex\":\"@inproceedings{\\n title = {Semantic search with domain-specific word-embedding and production monitoring in Fintech},\\n type = {inproceedings},\\n year = {2020},\\n pages = {28-33},\\n id = {90ca5cbd-dfdb-3fdc-8ef5-eccd9286f6b9},\\n created = {2020-12-07T09:11:03.324Z},\\n file_attached = {false},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2020-12-12T17:34:11.539Z},\\n read = {false},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\\n private_publication = {false},\\n bibtype = {inproceedings},\\n author = {Farmanbar, Mojtaba and Ommeren, Nikki Van and Zhao, Boyang},\\n booktitle = {Proceedings of the 28th International Conference on Computational Linguistics: System Demonstrations}\\n}\",\"author_short\":[\"Farmanbar,  M.\",\"Ommeren,  N., V.\",\"Zhao,  B.\"],\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"farmanbar-ommeren-zhao-semanticsearchwithdomainspecificwordembeddingandproductionmonitoringinfintech-2020\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Familial Hypercholesterolemia Identification Algorithm in Patients with Acute Cardiovascular Events in A Large Hospital Electronic Database in Bulgaria: A Call for Implementation\",\"type\":\"article\",\"year\":\"2021\",\"keywords\":\"Dutch l,Dyslipidemia,Familial hypercholesterolemia\",\"websites\":\"https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3\",\"month\":\"3\",\"publisher\":\"Springer Healthcare\",\"day\":\"23\",\"id\":\"8a897e7c-81b8-36f2-9578-71b2cbca7bbd\",\"created\":\"2021-03-23T11:16:36.146Z\",\"file_attached\":false,\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2021-03-23T12:20:16.891Z\",\"read\":false,\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"private_publication\":false,\"bibtype\":\"article\",\"author\":\"Petrov, Ivo and Postadzhiyan, Arman and Vasilev, Dobrin and Kasabov, Ruslan and Tokmakova, Mariya and Nikolov, Fedya and Istatkov, Veselin and Zhao, Boyang and Mutafchiev, Dimiter and Petkova, Reneta\",\"doi\":\"10.1007/s12325-020-01608-3\",\"journal\":\"Advances in Therapy\",\"bibtex\":\"@article{\\n title = {Familial Hypercholesterolemia Identification Algorithm in Patients with Acute Cardiovascular Events in A Large Hospital Electronic Database in Bulgaria: A Call for Implementation},\\n type = {article},\\n year = {2021},\\n keywords = {Dutch l,Dyslipidemia,Familial hypercholesterolemia},\\n websites = {https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3},\\n month = {3},\\n publisher = {Springer Healthcare},\\n day = {23},\\n id = {8a897e7c-81b8-36f2-9578-71b2cbca7bbd},\\n created = {2021-03-23T11:16:36.146Z},\\n file_attached = {false},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2021-03-23T12:20:16.891Z},\\n read = {false},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n private_publication = {false},\\n bibtype = {article},\\n author = {Petrov, Ivo and Postadzhiyan, Arman and Vasilev, Dobrin and Kasabov, Ruslan and Tokmakova, Mariya and Nikolov, Fedya and Istatkov, Veselin and Zhao, Boyang and Mutafchiev, Dimiter and Petkova, Reneta},\\n doi = {10.1007/s12325-020-01608-3},\\n journal = {Advances in Therapy}\\n}\",\"author_short\":[\"Petrov,  I.\",\"Postadzhiyan,  A.\",\"Vasilev,  D.\",\"Kasabov,  R.\",\"Tokmakova,  M.\",\"Nikolov,  F.\",\"Istatkov,  V.\",\"Zhao,  B.\",\"Mutafchiev,  D.\",\"Petkova,  R.\"],\"urls\":{\"Website\":\"https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"petrov-postadzhiyan-vasilev-kasabov-tokmakova-nikolov-istatkov-zhao-etal-familialhypercholesterolemiaidentificationalgorithminpatientswithacutecardiovasculareventsinalargehospitalelectronicdatabaseinbulgariaacallforimplementation-2021\",\"role\":\"author\",\"keyword\":[\"Dutch l\",\"Dyslipidemia\",\"Familial hypercholesterolemia\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution\",\"type\":\"article\",\"year\":\"2016\",\"pages\":\"234-246\",\"volume\":\"165\",\"websites\":\"http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599\",\"month\":\"3\",\"publisher\":\"Elsevier Inc.\",\"id\":\"51182afe-c562-3429-a6c1-e4fe1ebc201b\",\"created\":\"2021-03-28T17:21:31.269Z\",\"file_attached\":false,\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2021-05-16T17:36:41.576Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Zhao2016e\",\"folder_uuids\":\"7e96e842-b029-41e6-a73f-7511890cd62e\",\"private_publication\":false,\"abstract\":\"Summary The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities - A notion that we term \\\"temporal collateral sensitivity.\\\" Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph+ acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1-targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small-molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and Sedlak, Joseph C. and Srinivas, Raja and Creixell, Pau and Pritchard, Justin R. and Tidor, Bruce and Lauffenburger, Douglas A. and Hemann, Michael T.\",\"doi\":\"10.1016/j.cell.2016.01.045\",\"journal\":\"Cell\",\"number\":\"1\",\"keywords\":\"BCR-ABL1 inhibitor,cancer type: ALL,clonal evolution,collateral sensitivity,drug combination,drug resistance,mathematical modeling,tumor heterogeneity\",\"bibtex\":\"@article{\\n title = {Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution},\\n type = {article},\\n year = {2016},\\n pages = {234-246},\\n volume = {165},\\n websites = {http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599},\\n month = {3},\\n publisher = {Elsevier Inc.},\\n id = {51182afe-c562-3429-a6c1-e4fe1ebc201b},\\n created = {2021-03-28T17:21:31.269Z},\\n file_attached = {false},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2021-05-16T17:36:41.576Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Zhao2016e},\\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\\n private_publication = {false},\\n abstract = {Summary The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities - A notion that we term \\\"temporal collateral sensitivity.\\\" Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph+ acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1-targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small-molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities.},\\n bibtype = {article},\\n author = {Zhao, Boyang and Sedlak, Joseph C. and Srinivas, Raja and Creixell, Pau and Pritchard, Justin R. and Tidor, Bruce and Lauffenburger, Douglas A. and Hemann, Michael T.},\\n doi = {10.1016/j.cell.2016.01.045},\\n journal = {Cell},\\n number = {1},\\n keywords = {BCR-ABL1 inhibitor,cancer type: ALL,clonal evolution,collateral sensitivity,drug combination,drug resistance,mathematical modeling,tumor heterogeneity}\\n}\",\"author_short\":[\"Zhao,  B.\",\"Sedlak,  J., C.\",\"Srinivas,  R.\",\"Creixell,  P.\",\"Pritchard,  J., R.\",\"Tidor,  B.\",\"Lauffenburger,  D., A.\",\"Hemann,  M., T.\"],\"urls\":{\"Website\":\"http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-sedlak-srinivas-creixell-pritchard-tidor-lauffenburger-hemann-exploitingtemporalcollateralsensitivityintumorclonalevolution-2016\",\"role\":\"author\",\"keyword\":[\"BCR-ABL1 inhibitor\",\"cancer type: ALL\",\"clonal evolution\",\"collateral sensitivity\",\"drug combination\",\"drug resistance\",\"mathematical modeling\",\"tumor heterogeneity\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"Addressing genetic tumor heterogeneity through computationally predictive combination therapy.\",\"type\":\"article\",\"year\":\"2014\",\"pages\":\"166-74\",\"volume\":\"4\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/24318931\",\"month\":\"2\",\"day\":\"21\",\"id\":\"6c5074a4-d224-32d0-acba-ca3697dfb01d\",\"created\":\"2021-03-29T20:09:12.619Z\",\"accessed\":\"2014-06-18\",\"file_attached\":false,\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2021-03-29T20:09:17.701Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"citation_key\":\"Zhao2013\",\"folder_uuids\":\"7e96e842-b029-41e6-a73f-7511890cd62e\",\"private_publication\":false,\"abstract\":\"Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. We use RNA interference to model heterogeneous tumors, and demonstrate successful validation of computational predictions for how optimized drug combinations can yield superior effects on these tumors both in vitro and in vivo. Importantly, we discover here that for many such tumors knowledge of the predominant subpopulation is insufficient for determining the best drug combination. Surprisingly, in some cases, the optimal drug combination does not include drugs that would treat any particular subpopulation most effectively, challenging straightforward intuition. We confirm examples of such a case with survival studies in a murine preclinical lymphoma model. Altogether, our approach provides new insights about design principles for combination therapy in the context of intratumoral diversity, data that should inform the development of drug regimens superior for complex tumors. Significance: This study provides the first example of how combination drug regimens, using existing chemotherapies, can be rationally designed to maximize tumor cell death, while minimizing the outgrowth of clonal subpopulations.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and Pritchard, Justin R. and Lauffenburger, Douglas A. and Hemann, Michael T.\",\"doi\":\"10.1158/2159-8290.CD-13-0465\",\"journal\":\"Cancer discovery\",\"number\":\"2\",\"keywords\":\"drug combination,drug optimization,mathematical modeling,tumor heterogeneity\",\"bibtex\":\"@article{\\n title = {Addressing genetic tumor heterogeneity through computationally predictive combination therapy.},\\n type = {article},\\n year = {2014},\\n pages = {166-74},\\n volume = {4},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/24318931},\\n month = {2},\\n day = {21},\\n id = {6c5074a4-d224-32d0-acba-ca3697dfb01d},\\n created = {2021-03-29T20:09:12.619Z},\\n accessed = {2014-06-18},\\n file_attached = {false},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2021-03-29T20:09:17.701Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n citation_key = {Zhao2013},\\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\\n private_publication = {false},\\n abstract = {Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. We use RNA interference to model heterogeneous tumors, and demonstrate successful validation of computational predictions for how optimized drug combinations can yield superior effects on these tumors both in vitro and in vivo. Importantly, we discover here that for many such tumors knowledge of the predominant subpopulation is insufficient for determining the best drug combination. Surprisingly, in some cases, the optimal drug combination does not include drugs that would treat any particular subpopulation most effectively, challenging straightforward intuition. We confirm examples of such a case with survival studies in a murine preclinical lymphoma model. Altogether, our approach provides new insights about design principles for combination therapy in the context of intratumoral diversity, data that should inform the development of drug regimens superior for complex tumors. Significance: This study provides the first example of how combination drug regimens, using existing chemotherapies, can be rationally designed to maximize tumor cell death, while minimizing the outgrowth of clonal subpopulations.},\\n bibtype = {article},\\n author = {Zhao, Boyang and Pritchard, Justin R. and Lauffenburger, Douglas A. and Hemann, Michael T.},\\n doi = {10.1158/2159-8290.CD-13-0465},\\n journal = {Cancer discovery},\\n number = {2},\\n keywords = {drug combination,drug optimization,mathematical modeling,tumor heterogeneity}\\n}\",\"author_short\":[\"Zhao,  B.\",\"Pritchard,  J., R.\",\"Lauffenburger,  D., A.\",\"Hemann,  M., T.\"],\"urls\":{\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/24318931\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-pritchard-lauffenburger-hemann-addressinggenetictumorheterogeneitythroughcomputationallypredictivecombinationtherapy-2014\",\"role\":\"author\",\"keyword\":[\"drug combination\",\"drug optimization\",\"mathematical modeling\",\"tumor heterogeneity\"],\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"},{\"title\":\"A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments.\",\"type\":\"article\",\"year\":\"2022\",\"pages\":\"625\",\"volume\":\"13\",\"websites\":\"http://www.ncbi.nlm.nih.gov/pubmed/35110534\",\"publisher\":\"Springer US\",\"id\":\"cacce78a-2c7d-3dbe-8cdf-11526c63ce1a\",\"created\":\"2022-02-10T08:18:35.452Z\",\"file_attached\":false,\"profile_id\":\"3cf34896-6274-3001-ad57-9ba3f52c9235\",\"last_modified\":\"2022-03-26T18:37:28.712Z\",\"read\":\"true\",\"starred\":false,\"authored\":\"true\",\"confirmed\":\"true\",\"hidden\":false,\"folder_uuids\":\"7e96e842-b029-41e6-a73f-7511890cd62e\",\"private_publication\":false,\"abstract\":\"A genetic knockout can be lethal to one human cell type while increasing growth rate in another. This context specificity confounds genetic analysis and prevents reproducible genome engineering. Genome-wide CRISPR compendia across most common human cell lines offer the largest opportunity to understand the biology of cell specificity. The prevailing viewpoint, synthetic lethality, occurs when a genetic alteration creates a unique CRISPR dependency. Here, we use machine learning for an unbiased investigation of cell type specificity. Quantifying model accuracy, we find that most cell type specific phenotypes are predicted by the function of related genes of wild-type sequence, not synthetic lethal relationships. These models then identify unexpected sets of 100-300 genes where reduced CRISPR measurements can produce genome-scale loss-of-function predictions across >18,000 genes. Thus, it is possible to reduce in vitro CRISPR libraries by orders of magnitude—with some information loss—when we remove redundant genes and not redundant sgRNAs.\",\"bibtype\":\"article\",\"author\":\"Zhao, Boyang and Rao, Yiyun and Leighow, Scott and O'Brien, Edward P and Gilbert, Luke and Pritchard, Justin R\",\"doi\":\"10.1038/s41467-022-28045-w\",\"journal\":\"Nature communications\",\"number\":\"1\",\"bibtex\":\"@article{\\n title = {A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments.},\\n type = {article},\\n year = {2022},\\n pages = {625},\\n volume = {13},\\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/35110534},\\n publisher = {Springer US},\\n id = {cacce78a-2c7d-3dbe-8cdf-11526c63ce1a},\\n created = {2022-02-10T08:18:35.452Z},\\n file_attached = {false},\\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\\n last_modified = {2022-03-26T18:37:28.712Z},\\n read = {true},\\n starred = {false},\\n authored = {true},\\n confirmed = {true},\\n hidden = {false},\\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\\n private_publication = {false},\\n abstract = {A genetic knockout can be lethal to one human cell type while increasing growth rate in another. This context specificity confounds genetic analysis and prevents reproducible genome engineering. Genome-wide CRISPR compendia across most common human cell lines offer the largest opportunity to understand the biology of cell specificity. The prevailing viewpoint, synthetic lethality, occurs when a genetic alteration creates a unique CRISPR dependency. Here, we use machine learning for an unbiased investigation of cell type specificity. Quantifying model accuracy, we find that most cell type specific phenotypes are predicted by the function of related genes of wild-type sequence, not synthetic lethal relationships. These models then identify unexpected sets of 100-300 genes where reduced CRISPR measurements can produce genome-scale loss-of-function predictions across >18,000 genes. Thus, it is possible to reduce in vitro CRISPR libraries by orders of magnitude—with some information loss—when we remove redundant genes and not redundant sgRNAs.},\\n bibtype = {article},\\n author = {Zhao, Boyang and Rao, Yiyun and Leighow, Scott and O'Brien, Edward P and Gilbert, Luke and Pritchard, Justin R},\\n doi = {10.1038/s41467-022-28045-w},\\n journal = {Nature communications},\\n number = {1}\\n}\",\"author_short\":[\"Zhao,  B.\",\"Rao,  Y.\",\"Leighow,  S.\",\"O'Brien,  E., P.\",\"Gilbert,  L.\",\"Pritchard,  J., R.\"],\"urls\":{\"Website\":\"http://www.ncbi.nlm.nih.gov/pubmed/35110534\"},\"biburl\":\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235\",\"bibbaseid\":\"zhao-rao-leighow-obrien-gilbert-pritchard-apancrispranalysisofmammaliancellspecificityidentifiesultracompactsgrnasubsetsforgenomescaleexperiments-2022\",\"role\":\"author\",\"metadata\":{\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\"downloads\":0,\"html\":\"\"}],\n      metadata: {\"owner\":\"zhao,  b\",\"authorlinks\":{\"zhao,  b\":\"https://boyangzhao.github.io/publications/\"}},\n      ownerID: \"7YNQGNFDmvd67cvL5\"\n    };\n  </script>\n\n  <script type=\"text/javascript\">\n  var site$;\n  if (typeof $ != 'undefined') {\n    console.log('existing jquery: storing and then restoring');\n    site$ = $;\n    $ = null;\n  }\n  </script>\n\n  <script src=\"https://ajax.googleapis.com/ajax/libs/jquery/2.2.4/jquery.min.js\">\n  </script>\n  <script type=\"text/javascript\">\n  if (site$) {\n    console.log('existing jquery: avoiding conflict and restoring');\n    bb$ = $.noConflict(true);\n    $ = site$;\n  } else {\n    bb$ = $;\n  }\n  </script>\n\n  <script src=\"//bibbase.org/js/bibbase.min.js\"\n          type=\"text/javascript\">\n  </script>\n\n  <script type=\"text/javascript\"\n          src=\"https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.1/MathJax.js?config=TeX-AMS-MML_HTMLorMML\">\n  </script>\n  <script type=\"text/x-mathjax-config\">\n    MathJax.Hub.Config({tex2jax: {inlineMath: [['$','$'], ['\\\\(','\\\\)']]},\n                        skipTags: [\"body\"],\n                        processClass: \"bibbase_paper\"});\n  </script>\n\n  <style>\n  @media print {\n    .dontprint {\n        display: none !important;\n    }\n\n  .bibbase_group {\n    background-color: #E0E0E0;\n    font-style: italic;\n    font-size: larger;\n    text-shadow: 0px 0px 3px #FFFFFF;\n    border-radius: 4px 4px 4px 4px;\n    -moz-border-radius: 4px 4px 4px 4px;\n    -webkit-border-radius: 4px;\n    padding: 5px 40px 5px;\n    margin-top: 10px;\n    margin-bottom: 5px;\n    cursor: pointer;\n  }\n\n  .bibbase_paper {\n    margin-bottom: 5px;\n  }\n\n  }\n  </style>\n\n  \n  <div style=\"float: right; margin-right: 10px; margin-top: 10px; text-align: right; font-size: 12px\">\n    generated by\n    <a href=\"//bibbase.org\"\n       onclick=\"trackOutboundLink('bibbase', 'logo clicked', window.location.href, '//bibbase.org'); return false;\">\n      <img src=\"//bibbase.org/img/logo.svg\"\n           style=\"vertical-align: middle; margin-left: 3px; height: 16px;\"/\n           alt=\"bibbase.org\"\n           title=\"BibBase – The easiest way to maintain your publications page.\"\n        ></a>\n    \n  </div>\n  \n\n  <div id=\"bibbase_header\" class=\"dontprint\" style=\"\">\n\n    <ul class=\"nav nav-pills\" style=\"margin: 0px;\">\n\n      <li class=\"dropdown\" id=\"groupby_dropdown\">\n      <a class=\"dropdown-toggle\"\n         data-toggle=\"dropdown\"\n         href=\"#\">\n          Group by\n          <b class=\"caret\"></b>\n      </a>\n      <ul class=\"dropdown-menu\">\n        <li class=\"groupby year\"><a onclick=\"groupby('year')\">\n            Year</a>\n        </li>\n        <li class=\"groupby author\"><a onclick=\"groupby('author_short')\">\n            Author</a>\n        </li>\n        <li class=\"groupby type\"><a onclick=\"groupby('type')\">\n            Type</a>\n        </li>\n        <li class=\"groupby keyword\"><a onclick=\"groupby('keyword')\">\n            Keyword</a>\n        </li>\n        <li class=\"groupby downloads\"><a onclick=\"groupby('downloads')\">\n            Downloads</a>\n        </li>\n      </ul>\n      </li>\n\n\n      <li class=\"dropdown\" id=\"menu_dropdown\">\n      <a class=\"dropdown-toggle\"\n         data-toggle=\"dropdown\"\n         href=\"#\" alt=\"controls\">\n          <i class=\"fa fa-reorder\" alt=\"controls\"></i>\n          <b class=\"caret\"></b>\n      </a>\n      <ul class=\"dropdown-menu\">\n        <li>\n          <a onclick=\"toggleAll()\">\n            <i class=\"fa fa-chevron-down fa-fw\"></i> Expand/Collapse All\n          </a>\n        </li>\n        <li>\n          <a download=\"all.bib\" href=\"data:text/bibtex;base64,@article{
 title = {VIOLIN: vaccine investigation and online information network},
 type = {article},
 year = {2007},
 keywords = {database},
 pages = {D923-D928},
 volume = {36},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/18025042,https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm1039},
 month = {12},
 day = {23},
 id = {ac4d6ece-2838-3f27-bb85-0d27f2ac0bf7},
 created = {2009-08-22T08:04:52.000Z},
 accessed = {2011-05-21},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2018-02-17T12:57:12.685Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xiang2008},
 private_publication = {false},
 abstract = {Vaccines are among the most efficacious and cost-effective tools for reducing morbidity and mortality caused by infectious diseases. The vaccine investigation and online information network (VIOLIN) is a web-based central resource, allowing easy curation, comparison and analysis of vaccine-related research data across various human pathogens (e.g. Haemophilus influenzae, human immunodeficiency virus (HIV) and Plasmodium falciparum) of medical importance and across humans, other natural hosts and laboratory animals. Vaccine-related peer-reviewed literature data have been downloaded into the database from PubMed and are searchable through various literature search programs. Vaccine data are also annotated, edited and submitted to the database through a web-based interactive system that integrates efficient computational literature mining and accurate manual curation. Curated information includes general microbial pathogenesis and host protective immunity, vaccine preparation and characteristics, stimulated host responses after vaccination and protection efficacy after challenge. Vaccine-related pathogen and host genes are also annotated and available for searching through customized BLAST programs. All VIOLIN data are available for download in an eXtensible Markup Language (XML)-based data exchange format. VIOLIN is expected to become a centralized source of vaccine information and to provide investigators in basic and clinical sciences with curated data and bioinformatics tools for vaccine research and development. VIOLIN is publicly available at http://www.violinet.org.},
 bibtype = {article},
 author = {Xiang, Zuoshuang and Todd, Thomas and Ku, Kim P and Kovacic, Bethany L and Larson, Charles B and Chen, Fang and Hodges, Andrew P and Tian, Yuying and Olenzek, Elizabeth A and Zhao, Boyang and Colby, Lesley A and Rush, Howard G and Gilsdorf, Janet R and Jourdian, George W and He, Yongqun},
 doi = {10.1093/nar/gkm1039},
 journal = {Nucleic Acids Research},
 number = {Database}
}

@article{
 title = {Kinetic mechanism for the excision of hypoxanthine by Escherichia coli AlkA and evidence for binding to DNA ends.},
 type = {article},
 year = {2011},
 pages = {4350-9},
 volume = {50},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/21491902,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3098123},
 month = {5},
 day = {24},
 id = {2f72b967-3053-3dd8-924e-7d5f4f589512},
 created = {2011-05-22T00:54:50.000Z},
 accessed = {2011-04-16},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2021-03-28T17:21:31.527Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhao2011},
 private_publication = {false},
 abstract = {The Escherichia coli 3-methyladenine DNA glycosylase II protein (AlkA) recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair pathway. Although the enzyme was one of the first DNA repair glycosylases to be discovered more than 25 years ago and there are multiple crystal structures, the mechanism is poorly understood. Therefore, we have characterized the kinetic mechanism for the AlkA-catalyzed excision of the deaminated purine, hypoxanthine. The multiple-turnover glycosylase assays are consistent with Michaelis-Menten kinetics. However, under single-turnover conditions that are commonly employed for studying other DNA glycosylases, we observe an unusual biphasic protein saturation curve. Initially, the observed rate constant for excision increases with an increasing level of AlkA protein, but at higher protein concentrations, the rate constant decreases. This behavior can be most easily explained by tight binding to DNA ends and by crowding of multiple AlkA protamers on the DNA. Consistent with this model, crystal structures have shown the preferential binding of AlkA to DNA ends. By varying the position of the lesion, we identified an asymmetric substrate that does not show inhibition at higher concentrations of AlkA, and we performed pre-steady state and steady state kinetic analysis. Unlike the situation in other glycosylases, release of the abasic product is faster than N-glycosidic bond cleavage. Nevertheless, AlkA exhibits significant product inhibition under multiple-turnover conditions, and it binds approximately 10-fold more tightly to an abasic site than to a hypoxanthine lesion site. This tight binding could help protect abasic sites when the adaptive response to DNA alkylation is activated and very high levels of AlkA protein are present.},
 bibtype = {article},
 author = {Zhao, Boyang and O'Brien, Patrick John},
 doi = {10.1021/bi200232c},
 journal = {Biochemistry},
 number = {20}
}

@article{
 title = {Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination.},
 type = {article},
 year = {2012},
 pages = {C27-45},
 volume = {302},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/21940666},
 month = {1},
 id = {7957de91-72c5-3dc3-a353-168f8c9396ea},
 created = {2012-01-15T21:40:01.000Z},
 accessed = {2012-01-10},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2017-03-25T18:28:36.677Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhao2012},
 private_publication = {false},
 abstract = {Although extensive phosphoproteomic information is available for renal epithelial cells, previous emphasis has been on phosphorylation of serines and threonines with little focus on tyrosine phosphorylation. Here we have carried out large-scale identification of phosphotyrosine sites in pervanadate-treated native inner medullary collecting ducts of rat, with a view towards identification of physiological processes in epithelial cells that are potentially regulated by tyrosine phosphorylation. The method combined antibody-based affinity purification of tyrosine phosphorylated peptides coupled with immobilized metal ion chromatography to enrich tyrosine phosphopeptides, which were identified by LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins were identified. A large fraction of these sites have not been previously reported on standard phosphoproteomic databases. All results are accessible via an online database: http://helixweb.nih.gov/ESBL/Database/iPY/. Analysis of surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP, DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation. These motifs plus contextual information, integrated using the NetworKIN tool, suggest that the protein tyrosine kinases involved include members of the insulin- and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms and KEGG pathways whose protein elements are overrepresented in our data set point to structures involved in epithelial cell-cell and cell-matrix interactions ("adherens junction," "tight junction," and "focal adhesion") and to components of the actin cytoskeleton as major sites of tyrosine phosphorylation in these cells. In general, these findings mesh well with evidence that tyrosine phosphorylation plays a key role in epithelial polarity determination.},
 bibtype = {article},
 author = {Zhao, Boyang and Knepper, Mark A and Chou, Chung-Lin and Pisitkun, Trairak},
 doi = {10.1152/ajpcell.00300.2011},
 journal = {American journal of physiology. Cell physiology},
 number = {1}
}

@article{
 title = {CPhos: A program to calculate and visualize evolutionarily conserved functional phosphorylation sites.},
 type = {article},
 year = {2012},
 keywords = {bioinformatics,conservation,functional significance,information theory,phos-},
 pages = {3299-303},
 volume = {12},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/23001821},
 month = {11},
 day = {24},
 id = {c67c6412-4c88-3f86-b148-2518ab2bea53},
 created = {2012-11-29T12:49:09.000Z},
 accessed = {2012-11-29},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2017-03-25T18:28:36.677Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhao2012a},
 private_publication = {false},
 abstract = {Profiling using high-throughput MS has discovered an overwhelming number of novel protein phosphorylation sites ("phosphosites"). However, the functional relevance of these sites is not always clear. In light of recent studies on the evolutionary mechanism of phosphorylation, we have developed CPhos, a Java program that can assess the conservation of phosphosites among species using an information theory-based approach. The degree of conservation established using CPhos can be used to assess the functional significance of phosphosites. CPhos has a user friendly graphical user interface and is available both as a web service and as a standalone Java application to assist phosphoproteomic researchers in analyzing and prioritizing lists of phosphosites for further experimental validation. CPhos can be accessed or downloaded at http://helixweb.nih.gov/CPhos/.},
 bibtype = {article},
 author = {Zhao, Boyang and Pisitkun, Trairak and Hoffert, Jason D and Knepper, Mark a and Saeed, Fahad},
 doi = {10.1002/pmic.201200189},
 journal = {Proteomics},
 number = {22}
}

@article{
 title = {Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule.},
 type = {article},
 year = {2011},
 keywords = {Amino Acid Sequence,Animals,Chromatography,Distal,Distal: chemistry,Distal: cytology,Humans,Kidney Tubules,Liquid,Male,Membrane Proteins,Membrane Proteins: analysis,Membrane Proteins: genetics,Molecular Sequence Data,Phosphopeptides,Phosphopeptides: analysis,Phosphopeptides: genetics,Phosphoproteins,Phosphoproteins: analysis,Phosphoproteins: genetics,Protein Conformation,Protein Structure,Proteome,Proteome: analysis,Proximal,Proximal: chemistry,Proximal: cytology,Rats,Sequence Alignment,Sprague-Dawley,Tandem Mass Spectrometry,Tertiary},
 pages = {C755-70},
 volume = {300},
 websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3074622&tool=pmcentrez&rendertype=abstract},
 month = {4},
 id = {1473c45e-b556-3709-bde0-a19c51ec07ca},
 created = {2013-01-28T03:01:54.000Z},
 accessed = {2013-01-27},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2017-03-25T18:28:36.677Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Feric2011},
 private_publication = {false},
 abstract = {Recent advances in mass spectrometry (MS) have provided means for large-scale phosphoproteomic profiling of specific tissues. Here, we report results from large-scale tandem MS [liquid chromatography (LC)-MS/MS]-based phosphoproteomic profiling of biochemically isolated membranes from the renal cortex, with focus on transporters and regulatory proteins. Data sets were filtered (by target-decoy analysis) to limit false-positive identifications to <2%. A total of 7,125 unique nonphosphorylated and 743 unique phosphorylated peptides were identified. Among the phosphopeptides identified were sites on transporter proteins, i.e., solute carrier (Slc, n = 63), ATP-binding cassette (Abc, n = 4), and aquaporin (Aqp, n = 3) family proteins. Database searches reveal that a majority of the phosphorylation sites identified in transporter proteins were previously unreported. Most of the Slc family proteins are apical or basolateral transporters expressed in proximal tubule cells, including proteins known to mediate transport of glucose, amino acids, organic ions, and inorganic ions. In addition, we identified potentially important phosphorylation sites for transport proteins from distal nephron segments, including the bumetanide-sensitive Na-K-2Cl cotransporter (Slc12a1 or NKCC2) at Ser(87), Thr(101), and Ser(126) and the thiazide-sensitive Na-Cl cotransporter (Slc12a3 or NCC) at Ser(71) and Ser(124). A subset of phosphorylation sites in regulatory proteins coincided with known functional motifs, suggesting specific regulatory roles. An online database from this study (http://dir.nhlbi.nih.gov/papers/lkem/rcmpd/) provides a resource for future studies of transporter regulation.},
 bibtype = {article},
 author = {Feric, Marina and Zhao, Boyang and Hoffert, Jason D and Pisitkun, Trairak and Knepper, Mark A},
 doi = {10.1152/ajpcell.00360.2010},
 journal = {American journal of physiology. Cell physiology},
 number = {4}
}

@article{
 title = {Updates on the web-based VIOLIN vaccine database and analysis system.},
 type = {article},
 year = {2014},
 pages = {D1124-32},
 volume = {42},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/24259431},
 month = {1},
 day = {1},
 id = {03a23edb-5633-3c44-af14-a2e41fed35f1},
 created = {2014-03-06T08:30:02.000Z},
 accessed = {2014-01-22},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2017-03-25T18:28:36.677Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {He2014},
 private_publication = {false},
 abstract = {The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.},
 bibtype = {article},
 author = {He, Yongqun and Racz, Rebecca and Sayers, Samantha and Lin, Yu and Todd, Thomas and Hur, Junguk and Li, Xinna and Patel, Mukti and Zhao, Boyang and Chung, Monica and Ostrow, Joseph and Sylora, Andrew and Dungarani, Priya and Ulysse, Guerlain and Kochhar, Kanika and Vidri, Boris and Strait, Kelsey and Jourdian, George W and Xiang, Zuoshuang},
 doi = {10.1093/nar/gkt1133},
 journal = {Nucleic acids research},
 number = {1}
}

@article{
 title = {Intratumor heterogeneity alters most effective drugs in designed combinations.},
 type = {article},
 year = {2014},
 pages = {10773-8},
 volume = {111},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/25002493,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4115561&tool=pmcentrez&rendertype=abstract},
 month = {7},
 day = {22},
 id = {8eaa7f79-33fa-32db-b9fe-cd246ddc3e3b},
 created = {2014-08-03T05:54:23.000Z},
 accessed = {2014-08-18},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2017-03-25T18:28:36.677Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhao2014},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 abstract = {The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.},
 bibtype = {article},
 author = {Zhao, Boyang and Hemann, Michael T and Lauffenburger, Douglas A},
 doi = {10.1073/pnas.1323934111},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {29},
 keywords = {drug combination,drug optimization}
}

@article{
 title = {Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors},
 type = {article},
 year = {2015},
 keywords = {2015,2015 accepted,august 20,cancer,drug resistance,epigenetics,equally to this work,ezh2,july 17,mutation,published,received,september 02,these authors have contributed},
 volume = {6},
 websites = {http://www.oncotarget.com/abstract/5066},
 month = {10},
 day = {20},
 id = {67aa45a0-71bc-32f3-8fde-a581df0f0e1c},
 created = {2015-12-28T01:31:52.000Z},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2021-01-15T00:00:21.939Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Baker2015},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 bibtype = {article},
 author = {Baker, Theresa and Nerle, Sujata and Pritchard, Justin and Zhao, Boyang and Rivera, Victor M and Garner, Andrew and Gonzalvez, Francois},
 doi = {10.18632/oncotarget.5066},
 journal = {Oncotarget},
 number = {32}
}

@article{
 title = {Inherited Disease Genetics Improves the Identification of Cancer-Associated Genes},
 type = {article},
 year = {2016},
 pages = {e1006081},
 volume = {12},
 websites = {http://dx.plos.org/10.1371/journal.pgen.1006081},
 id = {66151242-3ddf-3a5f-ae08-636e44dcdf4f},
 created = {2016-06-18T05:46:23.000Z},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2021-01-16T10:42:35.904Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhao2016c},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 bibtype = {article},
 author = {Zhao, Boyang and Pritchard, Justin R.},
 doi = {10.1371/journal.pgen.1006081},
 journal = {PLoS Genetics},
 number = {6},
 keywords = {cancer driver identification,systems biology}
}

@article{
 title = {Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations},
 type = {article},
 year = {2016},
 pages = {36198},
 volume = {6},
 websites = {http://www.nature.com/articles/srep36198},
 publisher = {Nature Publishing Group},
 id = {10a79cac-8cf7-3d76-89f4-87f2a064a0cf},
 created = {2016-11-08T05:25:01.000Z},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2020-03-31T13:50:24.548Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Sun2016},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 bibtype = {article},
 author = {Sun, Daphne and Dalin, Simona and Hemann, Michael T. and Lauffenburger, Douglas A. and Zhao, Boyang},
 doi = {10.1038/srep36198},
 journal = {Scientific Reports},
 number = {October},
 keywords = {drug combination,drug resistance}
}

@article{
 title = {Modeling Tumor Clonal Evolution for Drug Combinations Design},
 type = {article},
 year = {2016},
 keywords = {clonal evolution,drug combination,drug optimization,drug resistance,drug scheduling,mathematical modeling,mathematical programming,review,tumor heterogeneity},
 pages = {144-158},
 volume = {2},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S2405803316000212},
 month = {3},
 publisher = {Elsevier Inc.},
 id = {605cd43c-a5e1-3fb2-92bb-c19d2f0430b0},
 created = {2017-04-12T01:29:39.680Z},
 file_attached = {true},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2017-10-27T16:11:01.757Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhao2016b},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 bibtype = {article},
 author = {Zhao, Boyang and Hemann, Michael T. and Lauffenburger, Douglas A.},
 doi = {10.1016/j.trecan.2016.02.001},
 journal = {Trends in Cancer},
 number = {3}
}

@article{
 title = {Clinical Data Extraction and Normalization of Cyrillic Electronic Health Records Via Deep-Learning Natural Language Processing.},
 type = {article},
 year = {2019},
 pages = {1-9},
 volume = {3},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/31577448},
 month = {9},
 id = {59dcce28-2d06-3c9b-bcf0-3effa4d08552},
 created = {2019-10-05T17:49:58.220Z},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2019-11-07T19:06:38.483Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 abstract = {PURPOSE A substantial portion of medical data is unstructured. Extracting data from unstructured text presents a barrier to advancing clinical research and improving patient care. In addition, ongoing studies have been focused predominately on the English language, whereas inflected languages with non-Latin alphabets (such as Slavic languages with a Cyrillic alphabet) present numerous linguistic challenges. We developed deep-learning-based natural language processing algorithms for automatically extracting biomarker status of patients with breast cancer from three oncology centers in Bulgaria. METHODS We used dual embeddings for English and Bulgarian languages, encoding both syntactic and polarity information for the words. The embeddings were subsequently aligned so that they were in the same vector space. The embeddings were used as input to convolutional or recurrent neural networks to derive the biomarker status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. RESULTS We showed that we can resolve ambiguity in highly variable medical text containing both Latin and Cyrillic text. Final models incorporating both English and Bulgarian syntax and polarity embeddings achieved F1 scores of 0.90 or higher for all estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 biomarkers. The models were robust against human errors originally found in the training set. In addition, such models can be extended for analyzing text containing words not seen during training. CONCLUSION By using several techniques that incorporate dual-word embeddings encoding syntactic and polarity information in two languages followed by deep neural network architectures, we show that researchers can extract and normalize parameters within medical data. The principles described here can be used to analyze Cyrillic or Latin mixed medical text and extract other parameters.},
 bibtype = {article},
 author = {Zhao, Boyang},
 doi = {10.1200/CCI.19.00057},
 journal = {JCO clinical cancer informatics},
 number = {2}
}

@article{
 title = {Evolution of the nonsense-mediated decay pathway is associated with decreased cytolytic immune infiltration.},
 type = {article},
 year = {2019},
 pages = {e1007467},
 volume = {15},
 websites = {http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270},
 month = {10},
 day = {28},
 id = {e4a1b363-f728-326d-973a-7e1cb778472c},
 created = {2019-11-07T19:06:38.129Z},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2021-01-16T10:42:35.980Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {The somatic co-evolution of tumors and the cellular immune responses that combat them drives the diversity of immune-tumor interactions. This includes tumor mutations that generate neo-antigenic epitopes that elicit cytotoxic T-cell activity and subsequent pressure to select for genetic loss of antigen presentation. Most studies have focused on how tumor missense mutations can drive tumor immunity, but frameshift mutations have the potential to create far greater antigenic diversity. However, expression of this antigenic diversity is potentially regulated by Nonsense Mediated Decay (NMD) and NMD has been shown to be of variable efficiency in cancers. Here we studied how mutational changes influence global NMD and cytolytic immune responses. Using TCGA datasets, we derived novel patient-level metrics of 'NMD burden' and interrogated how different mutation and most importantly NMD burdens influence cytolytic activity using machine learning models and survival outcomes. We find that NMD is a significant and independent predictor of immune cytolytic activity. Different indications exhibited varying dependence on NMD and mutation burden features. We also observed significant co-alteration of genes in the NMD pathway, with a global increase in NMD efficiency in patients with NMD co-alterations. Finally, NMD burden also stratified patient survival in multivariate regression models in subset of cancer types. Our work suggests that beyond selecting for mutations that elicit NMD in tumor suppressors, tumor evolution may react to the selective pressure generated by inflammation to globally enhance NMD through coordinated amplification and/or mutation.},
 bibtype = {article},
 author = {Zhao, Boyang and Pritchard, Justin R},
 doi = {10.1371/journal.pcbi.1007467},
 journal = {PLoS computational biology},
 number = {10}
}

@article{
 title = {Multi-scale Predictions of Drug Resistance Epidemiology Identify Design Principles for Rational Drug Design},
 type = {article},
 year = {2020},
 pages = {3951-3963.e4},
 volume = {30},
 websites = {https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898},
 month = {3},
 publisher = {ElsevierCompany.},
 id = {0269e27f-97b5-32f9-a162-754072105b5d},
 created = {2020-03-24T21:54:22.483Z},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2020-11-01T16:27:27.894Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Leighow, Scott M and Liu, Chuan and Inam, Haider and Zhao, Boyang and Pritchard, Justin R},
 doi = {10.1016/j.celrep.2020.02.108},
 journal = {Cell Reports},
 number = {12}
}

@inproceedings{
 title = {Semantic search with domain-specific word-embedding and production monitoring in Fintech},
 type = {inproceedings},
 year = {2020},
 pages = {28-33},
 id = {90ca5cbd-dfdb-3fdc-8ef5-eccd9286f6b9},
 created = {2020-12-07T09:11:03.324Z},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2020-12-12T17:34:11.539Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 bibtype = {inproceedings},
 author = {Farmanbar, Mojtaba and Ommeren, Nikki Van and Zhao, Boyang},
 booktitle = {Proceedings of the 28th International Conference on Computational Linguistics: System Demonstrations}
}

@article{
 title = {Familial Hypercholesterolemia Identification Algorithm in Patients with Acute Cardiovascular Events in A Large Hospital Electronic Database in Bulgaria: A Call for Implementation},
 type = {article},
 year = {2021},
 keywords = {Dutch l,Dyslipidemia,Familial hypercholesterolemia},
 websites = {https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3},
 month = {3},
 publisher = {Springer Healthcare},
 day = {23},
 id = {8a897e7c-81b8-36f2-9578-71b2cbca7bbd},
 created = {2021-03-23T11:16:36.146Z},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2021-03-23T12:20:16.891Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Petrov, Ivo and Postadzhiyan, Arman and Vasilev, Dobrin and Kasabov, Ruslan and Tokmakova, Mariya and Nikolov, Fedya and Istatkov, Veselin and Zhao, Boyang and Mutafchiev, Dimiter and Petkova, Reneta},
 doi = {10.1007/s12325-020-01608-3},
 journal = {Advances in Therapy}
}

@article{
 title = {Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution},
 type = {article},
 year = {2016},
 pages = {234-246},
 volume = {165},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599},
 month = {3},
 publisher = {Elsevier Inc.},
 id = {51182afe-c562-3429-a6c1-e4fe1ebc201b},
 created = {2021-03-28T17:21:31.269Z},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2021-05-16T17:36:41.576Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhao2016e},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 abstract = {Summary The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities - A notion that we term "temporal collateral sensitivity." Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph+ acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1-targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small-molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities.},
 bibtype = {article},
 author = {Zhao, Boyang and Sedlak, Joseph C. and Srinivas, Raja and Creixell, Pau and Pritchard, Justin R. and Tidor, Bruce and Lauffenburger, Douglas A. and Hemann, Michael T.},
 doi = {10.1016/j.cell.2016.01.045},
 journal = {Cell},
 number = {1},
 keywords = {BCR-ABL1 inhibitor,cancer type: ALL,clonal evolution,collateral sensitivity,drug combination,drug resistance,mathematical modeling,tumor heterogeneity}
}

@article{
 title = {Addressing genetic tumor heterogeneity through computationally predictive combination therapy.},
 type = {article},
 year = {2014},
 pages = {166-74},
 volume = {4},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/24318931},
 month = {2},
 day = {21},
 id = {6c5074a4-d224-32d0-acba-ca3697dfb01d},
 created = {2021-03-29T20:09:12.619Z},
 accessed = {2014-06-18},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2021-03-29T20:09:17.701Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhao2013},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 abstract = {Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. We use RNA interference to model heterogeneous tumors, and demonstrate successful validation of computational predictions for how optimized drug combinations can yield superior effects on these tumors both in vitro and in vivo. Importantly, we discover here that for many such tumors knowledge of the predominant subpopulation is insufficient for determining the best drug combination. Surprisingly, in some cases, the optimal drug combination does not include drugs that would treat any particular subpopulation most effectively, challenging straightforward intuition. We confirm examples of such a case with survival studies in a murine preclinical lymphoma model. Altogether, our approach provides new insights about design principles for combination therapy in the context of intratumoral diversity, data that should inform the development of drug regimens superior for complex tumors. Significance: This study provides the first example of how combination drug regimens, using existing chemotherapies, can be rationally designed to maximize tumor cell death, while minimizing the outgrowth of clonal subpopulations.},
 bibtype = {article},
 author = {Zhao, Boyang and Pritchard, Justin R. and Lauffenburger, Douglas A. and Hemann, Michael T.},
 doi = {10.1158/2159-8290.CD-13-0465},
 journal = {Cancer discovery},
 number = {2},
 keywords = {drug combination,drug optimization,mathematical modeling,tumor heterogeneity}
}

@article{
 title = {A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments.},
 type = {article},
 year = {2022},
 pages = {625},
 volume = {13},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/35110534},
 publisher = {Springer US},
 id = {cacce78a-2c7d-3dbe-8cdf-11526c63ce1a},
 created = {2022-02-10T08:18:35.452Z},
 file_attached = {false},
 profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},
 last_modified = {2022-03-26T18:37:28.712Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},
 private_publication = {false},
 abstract = {A genetic knockout can be lethal to one human cell type while increasing growth rate in another. This context specificity confounds genetic analysis and prevents reproducible genome engineering. Genome-wide CRISPR compendia across most common human cell lines offer the largest opportunity to understand the biology of cell specificity. The prevailing viewpoint, synthetic lethality, occurs when a genetic alteration creates a unique CRISPR dependency. Here, we use machine learning for an unbiased investigation of cell type specificity. Quantifying model accuracy, we find that most cell type specific phenotypes are predicted by the function of related genes of wild-type sequence, not synthetic lethal relationships. These models then identify unexpected sets of 100-300 genes where reduced CRISPR measurements can produce genome-scale loss-of-function predictions across >18,000 genes. Thus, it is possible to reduce in vitro CRISPR libraries by orders of magnitude—with some information loss—when we remove redundant genes and not redundant sgRNAs.},
 bibtype = {article},
 author = {Zhao, Boyang and Rao, Yiyun and Leighow, Scott and O'Brien, Edward P and Gilbert, Luke and Pritchard, Justin R},
 doi = {10.1038/s41467-022-28045-w},
 journal = {Nature communications},
 number = {1}
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To use this list on your own web site\n      or create a new web site from it,\n      <a href=\"/network/register?next=/network/newAccountWithFile%3FfileId=\"\n      >create a free account</a>. The file will be added\n      and you will be able to edit it in the File Manager.\n      We will show you instructions once you've created your account.\n    </div>\n\n    <div class=\"alert alert-warning bibbase_msg\" id=\"bibbase_msg_mendeley1\"\n         style=\"display: none;\">\n\n      <p>To the site owner:</p>\n\n      <p><strong>Action required!</strong> Mendeley is changing its\n        API. In order to keep using Mendeley with BibBase past April\n        14th, you need to:\n        <ol>\n          <li>renew the authorization for BibBase on Mendeley, and</li>\n          <li>update the BibBase URL\n            in your page the same way you did when you initially set up\n            this page.\n          </li>\n        </ol>\n      </p>\n\n      <p>\n        <a href=\"http://bibbase.org/cgi-bin/mendeley2/get.py\">\n          <i class=\"fa fa-angle-double-right\"></i>\n          Fix it now</a>\n      </p>\n    </div>\n\n  </div>\n\n\n  <div id=\"bibbase_body\">\n    \n  \n  <div class=\"bibbase_group_whole\" id=\"group_2022\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2022')\"\n      onkeypress=\"toggleGroup('group_2022')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2022</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"zhao-rao-leighow-obrien-gilbert-pritchard-apancrispranalysisofmammaliancellspecificityidentifiesultracompactsgrnasubsetsforgenomescaleexperiments-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/35110534\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-rao-leighow-obrien-gilbert-pritchard-apancrispranalysisofmammaliancellspecificityidentifiesultracompactsgrnasubsetsforgenomescaleexperiments-2022', 'http://www.ncbi.nlm.nih.gov/pubmed/35110534', event);\">\n    A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Rao,  Y.; Leighow,  S.; O'Brien,  E., P.; Gilbert,  L.;  and Pritchard,  J., R.\n</span>\n\n  \n\n</span>\n\n  <i>Nature communications</i>, 13(1): 625.  2022.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/35110534\"\n     onclick=\"log_download('zhao-rao-leighow-obrien-gilbert-pritchard-apancrispranalysisofmammaliancellspecificityidentifiesultracompactsgrnasubsetsforgenomescaleexperiments-2022', 'http://www.ncbi.nlm.nih.gov/pubmed/35110534', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1038/s41467-022-28045-w\"\n     onclick=\"log_download('zhao-rao-leighow-obrien-gilbert-pritchard-apancrispranalysisofmammaliancellspecificityidentifiesultracompactsgrnasubsetsforgenomescaleexperiments-2022', 'http://doi.org/10.1038/s41467-022-28045-w', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-rao-leighow-obrien-gilbert-pritchard-apancrispranalysisofmammaliancellspecificityidentifiesultracompactsgrnasubsetsforgenomescaleexperiments-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-rao-leighow-obrien-gilbert-pritchard-apancrispranalysisofmammaliancellspecificityidentifiesultracompactsgrnasubsetsforgenomescaleexperiments-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments.},\n type = {article},\n year = {2022},\n pages = {625},\n volume = {13},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/35110534},\n publisher = {Springer US},\n id = {cacce78a-2c7d-3dbe-8cdf-11526c63ce1a},\n created = {2022-02-10T08:18:35.452Z},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2022-03-26T18:37:28.712Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n abstract = {A genetic knockout can be lethal to one human cell type while increasing growth rate in another. This context specificity confounds genetic analysis and prevents reproducible genome engineering. Genome-wide CRISPR compendia across most common human cell lines offer the largest opportunity to understand the biology of cell specificity. The prevailing viewpoint, synthetic lethality, occurs when a genetic alteration creates a unique CRISPR dependency. Here, we use machine learning for an unbiased investigation of cell type specificity. Quantifying model accuracy, we find that most cell type specific phenotypes are predicted by the function of related genes of wild-type sequence, not synthetic lethal relationships. These models then identify unexpected sets of 100-300 genes where reduced CRISPR measurements can produce genome-scale loss-of-function predictions across &gt;18,000 genes. Thus, it is possible to reduce in vitro CRISPR libraries by orders of magnitude—with some information loss—when we remove redundant genes and not redundant sgRNAs.},\n bibtype = {article},\n author = {Zhao, Boyang and Rao, Yiyun and Leighow, Scott and O&#x27;Brien, Edward P and Gilbert, Luke and Pritchard, Justin R},\n doi = {10.1038/s41467-022-28045-w},\n journal = {Nature communications},\n number = {1}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  A genetic knockout can be lethal to one human cell type while increasing growth rate in another. This context specificity confounds genetic analysis and prevents reproducible genome engineering. Genome-wide CRISPR compendia across most common human cell lines offer the largest opportunity to understand the biology of cell specificity. The prevailing viewpoint, synthetic lethality, occurs when a genetic alteration creates a unique CRISPR dependency. Here, we use machine learning for an unbiased investigation of cell type specificity. Quantifying model accuracy, we find that most cell type specific phenotypes are predicted by the function of related genes of wild-type sequence, not synthetic lethal relationships. These models then identify unexpected sets of 100-300 genes where reduced CRISPR measurements can produce genome-scale loss-of-function predictions across >18,000 genes. Thus, it is possible to reduce in vitro CRISPR libraries by orders of magnitude—with some information loss—when we remove redundant genes and not redundant sgRNAs.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2021\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2021')\"\n      onkeypress=\"toggleGroup('group_2021')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2021</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"petrov-postadzhiyan-vasilev-kasabov-tokmakova-nikolov-istatkov-zhao-etal-familialhypercholesterolemiaidentificationalgorithminpatientswithacutecardiovasculareventsinalargehospitalelectronicdatabaseinbulgariaacallforimplementation-2021\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'petrov-postadzhiyan-vasilev-kasabov-tokmakova-nikolov-istatkov-zhao-etal-familialhypercholesterolemiaidentificationalgorithminpatientswithacutecardiovasculareventsinalargehospitalelectronicdatabaseinbulgariaacallforimplementation-2021', 'https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3', event);\">\n    Familial Hypercholesterolemia Identification Algorithm in Patients with Acute Cardiovascular Events in A Large Hospital Electronic Database in Bulgaria: A Call for Implementation.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Petrov,  I.; Postadzhiyan,  A.; Vasilev,  D.; Kasabov,  R.; Tokmakova,  M.; Nikolov,  F.; Istatkov,  V.; <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Mutafchiev,  D.;  and Petkova,  R.\n</span>\n\n  \n\n</span>\n\n  <i>Advances in Therapy</i>. 3 2021.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3\"\n     onclick=\"log_download('petrov-postadzhiyan-vasilev-kasabov-tokmakova-nikolov-istatkov-zhao-etal-familialhypercholesterolemiaidentificationalgorithminpatientswithacutecardiovasculareventsinalargehospitalelectronicdatabaseinbulgariaacallforimplementation-2021', 'https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Familial Hypercholesterolemia Identification Algorithm in Patients with Acute Cardiovascular Events in A Large Hospital Electronic Database in Bulgaria: A Call for Implementation [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s12325-020-01608-3\"\n     onclick=\"log_download('petrov-postadzhiyan-vasilev-kasabov-tokmakova-nikolov-istatkov-zhao-etal-familialhypercholesterolemiaidentificationalgorithminpatientswithacutecardiovasculareventsinalargehospitalelectronicdatabaseinbulgariaacallforimplementation-2021', 'http://doi.org/10.1007/s12325-020-01608-3', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/petrov-postadzhiyan-vasilev-kasabov-tokmakova-nikolov-istatkov-zhao-etal-familialhypercholesterolemiaidentificationalgorithminpatientswithacutecardiovasculareventsinalargehospitalelectronicdatabaseinbulgariaacallforimplementation-2021\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('petrov-postadzhiyan-vasilev-kasabov-tokmakova-nikolov-istatkov-zhao-etal-familialhypercholesterolemiaidentificationalgorithminpatientswithacutecardiovasculareventsinalargehospitalelectronicdatabaseinbulgariaacallforimplementation-2021')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Familial Hypercholesterolemia Identification Algorithm in Patients with Acute Cardiovascular Events in A Large Hospital Electronic Database in Bulgaria: A Call for Implementation},\n type = {article},\n year = {2021},\n keywords = {Dutch l,Dyslipidemia,Familial hypercholesterolemia},\n websites = {https://doi.org/10.1007/s12325-020-01608-3,http://link.springer.com/10.1007/s12325-020-01608-3},\n month = {3},\n publisher = {Springer Healthcare},\n day = {23},\n id = {8a897e7c-81b8-36f2-9578-71b2cbca7bbd},\n created = {2021-03-23T11:16:36.146Z},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2021-03-23T12:20:16.891Z},\n read = {false},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n bibtype = {article},\n author = {Petrov, Ivo and Postadzhiyan, Arman and Vasilev, Dobrin and Kasabov, Ruslan and Tokmakova, Mariya and Nikolov, Fedya and Istatkov, Veselin and Zhao, Boyang and Mutafchiev, Dimiter and Petkova, Reneta},\n doi = {10.1007/s12325-020-01608-3},\n journal = {Advances in Therapy}\n}</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2020\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2020')\"\n      onkeypress=\"toggleGroup('group_2020')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2020</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"leighow-liu-inam-zhao-pritchard-multiscalepredictionsofdrugresistanceepidemiologyidentifydesignprinciplesforrationaldrugdesign-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'leighow-liu-inam-zhao-pritchard-multiscalepredictionsofdrugresistanceepidemiologyidentifydesignprinciplesforrationaldrugdesign-2020', 'https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898', event);\">\n    Multi-scale Predictions of Drug Resistance Epidemiology Identify Design Principles for Rational Drug Design.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Leighow,  S., M.; Liu,  C.; Inam,  H.; <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>;  and Pritchard,  J., R.\n</span>\n\n  \n\n</span>\n\n  <i>Cell Reports</i>, 30(12): 3951-3963.e4. 3 2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898\"\n     onclick=\"log_download('leighow-liu-inam-zhao-pritchard-multiscalepredictionsofdrugresistanceepidemiologyidentifydesignprinciplesforrationaldrugdesign-2020', 'https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Multi-scale Predictions of Drug Resistance Epidemiology Identify Design Principles for Rational Drug Design [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.celrep.2020.02.108\"\n     onclick=\"log_download('leighow-liu-inam-zhao-pritchard-multiscalepredictionsofdrugresistanceepidemiologyidentifydesignprinciplesforrationaldrugdesign-2020', 'http://doi.org/10.1016/j.celrep.2020.02.108', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/leighow-liu-inam-zhao-pritchard-multiscalepredictionsofdrugresistanceepidemiologyidentifydesignprinciplesforrationaldrugdesign-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('leighow-liu-inam-zhao-pritchard-multiscalepredictionsofdrugresistanceepidemiologyidentifydesignprinciplesforrationaldrugdesign-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Multi-scale Predictions of Drug Resistance Epidemiology Identify Design Principles for Rational Drug Design},\n type = {article},\n year = {2020},\n pages = {3951-3963.e4},\n volume = {30},\n websites = {https://doi.org/10.1016/j.celrep.2020.02.108,https://linkinghub.elsevier.com/retrieve/pii/S2211124720302898},\n month = {3},\n publisher = {ElsevierCompany.},\n id = {0269e27f-97b5-32f9-a162-754072105b5d},\n created = {2020-03-24T21:54:22.483Z},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2020-11-01T16:27:27.894Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n bibtype = {article},\n author = {Leighow, Scott M and Liu, Chuan and Inam, Haider and Zhao, Boyang and Pritchard, Justin R},\n doi = {10.1016/j.celrep.2020.02.108},\n journal = {Cell Reports},\n number = {12}\n}</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"farmanbar-ommeren-zhao-semanticsearchwithdomainspecificwordembeddingandproductionmonitoringinfintech-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Semantic search with domain-specific word-embedding and production monitoring in Fintech.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Farmanbar,  M.; Ommeren,  N., V.;  and <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>\n</span>\n\n  \n\n</span>\n\n  In <i>Proceedings of the 28th International Conference on Computational Linguistics: System Demonstrations</i>, pages 28-33,  2020. \n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/farmanbar-ommeren-zhao-semanticsearchwithdomainspecificwordembeddingandproductionmonitoringinfintech-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('farmanbar-ommeren-zhao-semanticsearchwithdomainspecificwordembeddingandproductionmonitoringinfintech-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@inproceedings{\n title = {Semantic search with domain-specific word-embedding and production monitoring in Fintech},\n type = {inproceedings},\n year = {2020},\n pages = {28-33},\n id = {90ca5cbd-dfdb-3fdc-8ef5-eccd9286f6b9},\n created = {2020-12-07T09:11:03.324Z},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2020-12-12T17:34:11.539Z},\n read = {false},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n bibtype = {inproceedings},\n author = {Farmanbar, Mojtaba and Ommeren, Nikki Van and Zhao, Boyang},\n booktitle = {Proceedings of the 28th International Conference on Computational Linguistics: System Demonstrations}\n}</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2019\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2019')\"\n      onkeypress=\"toggleGroup('group_2019')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2019</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"zhao-clinicaldataextractionandnormalizationofcyrillicelectronichealthrecordsviadeeplearningnaturallanguageprocessing-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31577448\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-clinicaldataextractionandnormalizationofcyrillicelectronichealthrecordsviadeeplearningnaturallanguageprocessing-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/31577448', event);\">\n    Clinical Data Extraction and Normalization of Cyrillic Electronic Health Records Via Deep-Learning Natural Language Processing.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>\n</span>\n\n  \n\n</span>\n\n  <i>JCO clinical cancer informatics</i>, 3(2): 1-9. 9 2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/31577448\"\n     onclick=\"log_download('zhao-clinicaldataextractionandnormalizationofcyrillicelectronichealthrecordsviadeeplearningnaturallanguageprocessing-2019', 'http://www.ncbi.nlm.nih.gov/pubmed/31577448', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Clinical Data Extraction and Normalization of Cyrillic Electronic Health Records Via Deep-Learning Natural Language Processing. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1200/CCI.19.00057\"\n     onclick=\"log_download('zhao-clinicaldataextractionandnormalizationofcyrillicelectronichealthrecordsviadeeplearningnaturallanguageprocessing-2019', 'http://doi.org/10.1200/CCI.19.00057', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-clinicaldataextractionandnormalizationofcyrillicelectronichealthrecordsviadeeplearningnaturallanguageprocessing-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-clinicaldataextractionandnormalizationofcyrillicelectronichealthrecordsviadeeplearningnaturallanguageprocessing-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Clinical Data Extraction and Normalization of Cyrillic Electronic Health Records Via Deep-Learning Natural Language Processing.},\n type = {article},\n year = {2019},\n pages = {1-9},\n volume = {3},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/31577448},\n month = {9},\n id = {59dcce28-2d06-3c9b-bcf0-3effa4d08552},\n created = {2019-10-05T17:49:58.220Z},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2019-11-07T19:06:38.483Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n abstract = {PURPOSE A substantial portion of medical data is unstructured. Extracting data from unstructured text presents a barrier to advancing clinical research and improving patient care. In addition, ongoing studies have been focused predominately on the English language, whereas inflected languages with non-Latin alphabets (such as Slavic languages with a Cyrillic alphabet) present numerous linguistic challenges. We developed deep-learning-based natural language processing algorithms for automatically extracting biomarker status of patients with breast cancer from three oncology centers in Bulgaria. METHODS We used dual embeddings for English and Bulgarian languages, encoding both syntactic and polarity information for the words. The embeddings were subsequently aligned so that they were in the same vector space. The embeddings were used as input to convolutional or recurrent neural networks to derive the biomarker status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. RESULTS We showed that we can resolve ambiguity in highly variable medical text containing both Latin and Cyrillic text. Final models incorporating both English and Bulgarian syntax and polarity embeddings achieved F1 scores of 0.90 or higher for all estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 biomarkers. The models were robust against human errors originally found in the training set. In addition, such models can be extended for analyzing text containing words not seen during training. CONCLUSION By using several techniques that incorporate dual-word embeddings encoding syntactic and polarity information in two languages followed by deep neural network architectures, we show that researchers can extract and normalize parameters within medical data. The principles described here can be used to analyze Cyrillic or Latin mixed medical text and extract other parameters.},\n bibtype = {article},\n author = {Zhao, Boyang},\n doi = {10.1200/CCI.19.00057},\n journal = {JCO clinical cancer informatics},\n number = {2}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  PURPOSE A substantial portion of medical data is unstructured. Extracting data from unstructured text presents a barrier to advancing clinical research and improving patient care. In addition, ongoing studies have been focused predominately on the English language, whereas inflected languages with non-Latin alphabets (such as Slavic languages with a Cyrillic alphabet) present numerous linguistic challenges. We developed deep-learning-based natural language processing algorithms for automatically extracting biomarker status of patients with breast cancer from three oncology centers in Bulgaria. METHODS We used dual embeddings for English and Bulgarian languages, encoding both syntactic and polarity information for the words. The embeddings were subsequently aligned so that they were in the same vector space. The embeddings were used as input to convolutional or recurrent neural networks to derive the biomarker status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. RESULTS We showed that we can resolve ambiguity in highly variable medical text containing both Latin and Cyrillic text. Final models incorporating both English and Bulgarian syntax and polarity embeddings achieved F1 scores of 0.90 or higher for all estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 biomarkers. The models were robust against human errors originally found in the training set. In addition, such models can be extended for analyzing text containing words not seen during training. CONCLUSION By using several techniques that incorporate dual-word embeddings encoding syntactic and polarity information in two languages followed by deep neural network architectures, we show that researchers can extract and normalize parameters within medical data. The principles described here can be used to analyze Cyrillic or Latin mixed medical text and extract other parameters.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhao-pritchard-evolutionofthenonsensemediateddecaypathwayisassociatedwithdecreasedcytolyticimmuneinfiltration-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-pritchard-evolutionofthenonsensemediateddecaypathwayisassociatedwithdecreasedcytolyticimmuneinfiltration-2019', 'http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270', event);\">\n    Evolution of the nonsense-mediated decay pathway is associated with decreased cytolytic immune infiltration.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>;  and Pritchard,  J., R.\n</span>\n\n  \n\n</span>\n\n  <i>PLoS computational biology</i>, 15(10): e1007467. 10 2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270\"\n     onclick=\"log_download('zhao-pritchard-evolutionofthenonsensemediateddecaypathwayisassociatedwithdecreasedcytolyticimmuneinfiltration-2019', 'http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Evolution of the nonsense-mediated decay pathway is associated with decreased cytolytic immune infiltration. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1371/journal.pcbi.1007467\"\n     onclick=\"log_download('zhao-pritchard-evolutionofthenonsensemediateddecaypathwayisassociatedwithdecreasedcytolyticimmuneinfiltration-2019', 'http://doi.org/10.1371/journal.pcbi.1007467', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-pritchard-evolutionofthenonsensemediateddecaypathwayisassociatedwithdecreasedcytolyticimmuneinfiltration-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-pritchard-evolutionofthenonsensemediateddecaypathwayisassociatedwithdecreasedcytolyticimmuneinfiltration-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Evolution of the nonsense-mediated decay pathway is associated with decreased cytolytic immune infiltration.},\n type = {article},\n year = {2019},\n pages = {e1007467},\n volume = {15},\n websites = {http://biorxiv.org/content/early/2019/02/04/535773.abstract,http://www.ncbi.nlm.nih.gov/pubmed/31658270},\n month = {10},\n day = {28},\n id = {e4a1b363-f728-326d-973a-7e1cb778472c},\n created = {2019-11-07T19:06:38.129Z},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2021-01-16T10:42:35.980Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n abstract = {The somatic co-evolution of tumors and the cellular immune responses that combat them drives the diversity of immune-tumor interactions. This includes tumor mutations that generate neo-antigenic epitopes that elicit cytotoxic T-cell activity and subsequent pressure to select for genetic loss of antigen presentation. Most studies have focused on how tumor missense mutations can drive tumor immunity, but frameshift mutations have the potential to create far greater antigenic diversity. However, expression of this antigenic diversity is potentially regulated by Nonsense Mediated Decay (NMD) and NMD has been shown to be of variable efficiency in cancers. Here we studied how mutational changes influence global NMD and cytolytic immune responses. Using TCGA datasets, we derived novel patient-level metrics of &#x27;NMD burden&#x27; and interrogated how different mutation and most importantly NMD burdens influence cytolytic activity using machine learning models and survival outcomes. We find that NMD is a significant and independent predictor of immune cytolytic activity. Different indications exhibited varying dependence on NMD and mutation burden features. We also observed significant co-alteration of genes in the NMD pathway, with a global increase in NMD efficiency in patients with NMD co-alterations. Finally, NMD burden also stratified patient survival in multivariate regression models in subset of cancer types. Our work suggests that beyond selecting for mutations that elicit NMD in tumor suppressors, tumor evolution may react to the selective pressure generated by inflammation to globally enhance NMD through coordinated amplification and/or mutation.},\n bibtype = {article},\n author = {Zhao, Boyang and Pritchard, Justin R},\n doi = {10.1371/journal.pcbi.1007467},\n journal = {PLoS computational biology},\n number = {10}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The somatic co-evolution of tumors and the cellular immune responses that combat them drives the diversity of immune-tumor interactions. This includes tumor mutations that generate neo-antigenic epitopes that elicit cytotoxic T-cell activity and subsequent pressure to select for genetic loss of antigen presentation. Most studies have focused on how tumor missense mutations can drive tumor immunity, but frameshift mutations have the potential to create far greater antigenic diversity. However, expression of this antigenic diversity is potentially regulated by Nonsense Mediated Decay (NMD) and NMD has been shown to be of variable efficiency in cancers. Here we studied how mutational changes influence global NMD and cytolytic immune responses. Using TCGA datasets, we derived novel patient-level metrics of 'NMD burden' and interrogated how different mutation and most importantly NMD burdens influence cytolytic activity using machine learning models and survival outcomes. We find that NMD is a significant and independent predictor of immune cytolytic activity. Different indications exhibited varying dependence on NMD and mutation burden features. We also observed significant co-alteration of genes in the NMD pathway, with a global increase in NMD efficiency in patients with NMD co-alterations. Finally, NMD burden also stratified patient survival in multivariate regression models in subset of cancer types. Our work suggests that beyond selecting for mutations that elicit NMD in tumor suppressors, tumor evolution may react to the selective pressure generated by inflammation to globally enhance NMD through coordinated amplification and/or mutation.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2016\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2016')\"\n      onkeypress=\"toggleGroup('group_2016')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2016</span>\n      <span class=\"bibbase_group_count\">\n        \n        (4)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"zhao-pritchard-inheriteddiseasegeneticsimprovestheidentificationofcancerassociatedgenes-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/66c7ef86-6636-e71d-072f-4a6c778f88a9/2016-Inherited_Disease_Genetics_Improves_the_Identification_of_Cancer-Associated_Genes.pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-pritchard-inheriteddiseasegeneticsimprovestheidentificationofcancerassociatedgenes-2016', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/66c7ef86-6636-e71d-072f-4a6c778f88a9/2016-Inherited_Disease_Genetics_Improves_the_Identification_of_Cancer-Associated_Genes.pdf.pdf', event);\">\n    Inherited Disease Genetics Improves the Identification of Cancer-Associated Genes.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>;  and Pritchard,  J., R.\n</span>\n\n  \n\n</span>\n\n  <i>PLoS Genetics</i>, 12(6): e1006081.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/66c7ef86-6636-e71d-072f-4a6c778f88a9/2016-Inherited_Disease_Genetics_Improves_the_Identification_of_Cancer-Associated_Genes.pdf.pdf\"\n     onclick=\"log_download('zhao-pritchard-inheriteddiseasegeneticsimprovestheidentificationofcancerassociatedgenes-2016', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/66c7ef86-6636-e71d-072f-4a6c778f88a9/2016-Inherited_Disease_Genetics_Improves_the_Identification_of_Cancer-Associated_Genes.pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Inherited Disease Genetics Improves the Identification of Cancer-Associated Genes [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://dx.plos.org/10.1371/journal.pgen.1006081\"\n     onclick=\"log_download('zhao-pritchard-inheriteddiseasegeneticsimprovestheidentificationofcancerassociatedgenes-2016', 'http://dx.plos.org/10.1371/journal.pgen.1006081', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Inherited Disease Genetics Improves the Identification of Cancer-Associated Genes [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1371/journal.pgen.1006081\"\n     onclick=\"log_download('zhao-pritchard-inheriteddiseasegeneticsimprovestheidentificationofcancerassociatedgenes-2016', 'http://doi.org/10.1371/journal.pgen.1006081', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-pritchard-inheriteddiseasegeneticsimprovestheidentificationofcancerassociatedgenes-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-pritchard-inheriteddiseasegeneticsimprovestheidentificationofcancerassociatedgenes-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Inherited Disease Genetics Improves the Identification of Cancer-Associated Genes},\n type = {article},\n year = {2016},\n pages = {e1006081},\n volume = {12},\n websites = {http://dx.plos.org/10.1371/journal.pgen.1006081},\n id = {66151242-3ddf-3a5f-ae08-636e44dcdf4f},\n created = {2016-06-18T05:46:23.000Z},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2021-01-16T10:42:35.904Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Zhao2016c},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n bibtype = {article},\n author = {Zhao, Boyang and Pritchard, Justin R.},\n doi = {10.1371/journal.pgen.1006081},\n journal = {PLoS Genetics},\n number = {6},\n keywords = {cancer driver identification,systems biology}\n}</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"sun-dalin-hemann-lauffenburger-zhao-differentialselectivepressurealtersrateofdrugresistanceacquisitioninheterogeneoustumorpopulations-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/01953cb5-363c-6413-436a-9c6e5dd32945/Sun_2016_Sci_Rep___differential_selective_pressure_alter_drug_resistance_rate.pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'sun-dalin-hemann-lauffenburger-zhao-differentialselectivepressurealtersrateofdrugresistanceacquisitioninheterogeneoustumorpopulations-2016', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/01953cb5-363c-6413-436a-9c6e5dd32945/Sun_2016_Sci_Rep___differential_selective_pressure_alter_drug_resistance_rate.pdf.pdf', event);\">\n    Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Sun,  D.; Dalin,  S.; Hemann,  M., T.; Lauffenburger,  D., A.;  and <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Scientific Reports</i>, 6(October): 36198.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/01953cb5-363c-6413-436a-9c6e5dd32945/Sun_2016_Sci_Rep___differential_selective_pressure_alter_drug_resistance_rate.pdf.pdf\"\n     onclick=\"log_download('sun-dalin-hemann-lauffenburger-zhao-differentialselectivepressurealtersrateofdrugresistanceacquisitioninheterogeneoustumorpopulations-2016', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/01953cb5-363c-6413-436a-9c6e5dd32945/Sun_2016_Sci_Rep___differential_selective_pressure_alter_drug_resistance_rate.pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://www.nature.com/articles/srep36198\"\n     onclick=\"log_download('sun-dalin-hemann-lauffenburger-zhao-differentialselectivepressurealtersrateofdrugresistanceacquisitioninheterogeneoustumorpopulations-2016', 'http://www.nature.com/articles/srep36198', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1038/srep36198\"\n     onclick=\"log_download('sun-dalin-hemann-lauffenburger-zhao-differentialselectivepressurealtersrateofdrugresistanceacquisitioninheterogeneoustumorpopulations-2016', 'http://doi.org/10.1038/srep36198', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/sun-dalin-hemann-lauffenburger-zhao-differentialselectivepressurealtersrateofdrugresistanceacquisitioninheterogeneoustumorpopulations-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('sun-dalin-hemann-lauffenburger-zhao-differentialselectivepressurealtersrateofdrugresistanceacquisitioninheterogeneoustumorpopulations-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations},\n type = {article},\n year = {2016},\n pages = {36198},\n volume = {6},\n websites = {http://www.nature.com/articles/srep36198},\n publisher = {Nature Publishing Group},\n id = {10a79cac-8cf7-3d76-89f4-87f2a064a0cf},\n created = {2016-11-08T05:25:01.000Z},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2020-03-31T13:50:24.548Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Sun2016},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n bibtype = {article},\n author = {Sun, Daphne and Dalin, Simona and Hemann, Michael T. and Lauffenburger, Douglas A. and Zhao, Boyang},\n doi = {10.1038/srep36198},\n journal = {Scientific Reports},\n number = {October},\n keywords = {drug combination,drug resistance}\n}</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhao-hemann-lauffenburger-modelingtumorclonalevolutionfordrugcombinationsdesign-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/429fb4d5-10e7-57a5-5565-934956e4743c/Zhao_2016_Trends_Cancer___review_modeling_tumor_clonal_evolution_for_drug_combinations.pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-hemann-lauffenburger-modelingtumorclonalevolutionfordrugcombinationsdesign-2016', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/429fb4d5-10e7-57a5-5565-934956e4743c/Zhao_2016_Trends_Cancer___review_modeling_tumor_clonal_evolution_for_drug_combinations.pdf.pdf', event);\">\n    Modeling Tumor Clonal Evolution for Drug Combinations Design.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Hemann,  M., T.;  and Lauffenburger,  D., A.\n</span>\n\n  \n\n</span>\n\n  <i>Trends in Cancer</i>, 2(3): 144-158. 3 2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/429fb4d5-10e7-57a5-5565-934956e4743c/Zhao_2016_Trends_Cancer___review_modeling_tumor_clonal_evolution_for_drug_combinations.pdf.pdf\"\n     onclick=\"log_download('zhao-hemann-lauffenburger-modelingtumorclonalevolutionfordrugcombinationsdesign-2016', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/429fb4d5-10e7-57a5-5565-934956e4743c/Zhao_2016_Trends_Cancer___review_modeling_tumor_clonal_evolution_for_drug_combinations.pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Modeling Tumor Clonal Evolution for Drug Combinations Design [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://linkinghub.elsevier.com/retrieve/pii/S2405803316000212\"\n     onclick=\"log_download('zhao-hemann-lauffenburger-modelingtumorclonalevolutionfordrugcombinationsdesign-2016', 'http://linkinghub.elsevier.com/retrieve/pii/S2405803316000212', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Modeling Tumor Clonal Evolution for Drug Combinations Design [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.trecan.2016.02.001\"\n     onclick=\"log_download('zhao-hemann-lauffenburger-modelingtumorclonalevolutionfordrugcombinationsdesign-2016', 'http://doi.org/10.1016/j.trecan.2016.02.001', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-hemann-lauffenburger-modelingtumorclonalevolutionfordrugcombinationsdesign-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-hemann-lauffenburger-modelingtumorclonalevolutionfordrugcombinationsdesign-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Modeling Tumor Clonal Evolution for Drug Combinations Design},\n type = {article},\n year = {2016},\n keywords = {clonal evolution,drug combination,drug optimization,drug resistance,drug scheduling,mathematical modeling,mathematical programming,review,tumor heterogeneity},\n pages = {144-158},\n volume = {2},\n websites = {http://linkinghub.elsevier.com/retrieve/pii/S2405803316000212},\n month = {3},\n publisher = {Elsevier Inc.},\n id = {605cd43c-a5e1-3fb2-92bb-c19d2f0430b0},\n created = {2017-04-12T01:29:39.680Z},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2017-10-27T16:11:01.757Z},\n read = {false},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Zhao2016b},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n bibtype = {article},\n author = {Zhao, Boyang and Hemann, Michael T. and Lauffenburger, Douglas A.},\n doi = {10.1016/j.trecan.2016.02.001},\n journal = {Trends in Cancer},\n number = {3}\n}</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhao-sedlak-srinivas-creixell-pritchard-tidor-lauffenburger-hemann-exploitingtemporalcollateralsensitivityintumorclonalevolution-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-sedlak-srinivas-creixell-pritchard-tidor-lauffenburger-hemann-exploitingtemporalcollateralsensitivityintumorclonalevolution-2016', 'http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599', event);\">\n    Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Sedlak,  J., C.; Srinivas,  R.; Creixell,  P.; Pritchard,  J., R.; Tidor,  B.; Lauffenburger,  D., A.;  and Hemann,  M., T.\n</span>\n\n  \n\n</span>\n\n  <i>Cell</i>, 165(1): 234-246. 3 2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599\"\n     onclick=\"log_download('zhao-sedlak-srinivas-creixell-pritchard-tidor-lauffenburger-hemann-exploitingtemporalcollateralsensitivityintumorclonalevolution-2016', 'http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.cell.2016.01.045\"\n     onclick=\"log_download('zhao-sedlak-srinivas-creixell-pritchard-tidor-lauffenburger-hemann-exploitingtemporalcollateralsensitivityintumorclonalevolution-2016', 'http://doi.org/10.1016/j.cell.2016.01.045', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-sedlak-srinivas-creixell-pritchard-tidor-lauffenburger-hemann-exploitingtemporalcollateralsensitivityintumorclonalevolution-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-sedlak-srinivas-creixell-pritchard-tidor-lauffenburger-hemann-exploitingtemporalcollateralsensitivityintumorclonalevolution-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution},\n type = {article},\n year = {2016},\n pages = {234-246},\n volume = {165},\n websites = {http://linkinghub.elsevier.com/retrieve/pii/S0092867416300599,http://dx.doi.org/10.1016/j.cell.2016.01.045,https://linkinghub.elsevier.com/retrieve/pii/S0092867416300599},\n month = {3},\n publisher = {Elsevier Inc.},\n id = {51182afe-c562-3429-a6c1-e4fe1ebc201b},\n created = {2021-03-28T17:21:31.269Z},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2021-05-16T17:36:41.576Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Zhao2016e},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n abstract = {Summary The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities - A notion that we term &quot;temporal collateral sensitivity.&quot; Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph+ acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1-targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small-molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities.},\n bibtype = {article},\n author = {Zhao, Boyang and Sedlak, Joseph C. and Srinivas, Raja and Creixell, Pau and Pritchard, Justin R. and Tidor, Bruce and Lauffenburger, Douglas A. and Hemann, Michael T.},\n doi = {10.1016/j.cell.2016.01.045},\n journal = {Cell},\n number = {1},\n keywords = {BCR-ABL1 inhibitor,cancer type: ALL,clonal evolution,collateral sensitivity,drug combination,drug resistance,mathematical modeling,tumor heterogeneity}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Summary The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities - A notion that we term \"temporal collateral sensitivity.\" Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph+ acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1-targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small-molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2015\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2015')\"\n      onkeypress=\"toggleGroup('group_2015')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2015</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"baker-nerle-pritchard-zhao-rivera-garner-gonzalvez-acquisitionofasingleezh2d1domainmutationconfersacquiredresistancetoezh2targetedinhibitors-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.oncotarget.com/abstract/5066\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'baker-nerle-pritchard-zhao-rivera-garner-gonzalvez-acquisitionofasingleezh2d1domainmutationconfersacquiredresistancetoezh2targetedinhibitors-2015', 'http://www.oncotarget.com/abstract/5066', event);\">\n    Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Baker,  T.; Nerle,  S.; Pritchard,  J.; <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Rivera,  V., M.; Garner,  A.;  and Gonzalvez,  F.\n</span>\n\n  \n\n</span>\n\n  <i>Oncotarget</i>, 6(32). 10 2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.oncotarget.com/abstract/5066\"\n     onclick=\"log_download('baker-nerle-pritchard-zhao-rivera-garner-gonzalvez-acquisitionofasingleezh2d1domainmutationconfersacquiredresistancetoezh2targetedinhibitors-2015', 'http://www.oncotarget.com/abstract/5066', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.18632/oncotarget.5066\"\n     onclick=\"log_download('baker-nerle-pritchard-zhao-rivera-garner-gonzalvez-acquisitionofasingleezh2d1domainmutationconfersacquiredresistancetoezh2targetedinhibitors-2015', 'http://doi.org/10.18632/oncotarget.5066', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/baker-nerle-pritchard-zhao-rivera-garner-gonzalvez-acquisitionofasingleezh2d1domainmutationconfersacquiredresistancetoezh2targetedinhibitors-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('baker-nerle-pritchard-zhao-rivera-garner-gonzalvez-acquisitionofasingleezh2d1domainmutationconfersacquiredresistancetoezh2targetedinhibitors-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors},\n type = {article},\n year = {2015},\n keywords = {2015,2015 accepted,august 20,cancer,drug resistance,epigenetics,equally to this work,ezh2,july 17,mutation,published,received,september 02,these authors have contributed},\n volume = {6},\n websites = {http://www.oncotarget.com/abstract/5066},\n month = {10},\n day = {20},\n id = {67aa45a0-71bc-32f3-8fde-a581df0f0e1c},\n created = {2015-12-28T01:31:52.000Z},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2021-01-15T00:00:21.939Z},\n read = {false},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Baker2015},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n bibtype = {article},\n author = {Baker, Theresa and Nerle, Sujata and Pritchard, Justin and Zhao, Boyang and Rivera, Victor M and Garner, Andrew and Gonzalvez, Francois},\n doi = {10.18632/oncotarget.5066},\n journal = {Oncotarget},\n number = {32}\n}</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2014\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2014')\"\n      onkeypress=\"toggleGroup('group_2014')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2014</span>\n      <span class=\"bibbase_group_count\">\n        \n        (3)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"he-racz-sayers-lin-todd-hur-li-patel-etal-updatesonthewebbasedviolinvaccinedatabaseandanalysissystem-2014\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6b25c1e8-a4f7-8e1b-529e-7c227d53d087/2014-Updates_on_the_web-based_VIOLIN_vaccine_database_and_analysis_system..pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'he-racz-sayers-lin-todd-hur-li-patel-etal-updatesonthewebbasedviolinvaccinedatabaseandanalysissystem-2014', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6b25c1e8-a4f7-8e1b-529e-7c227d53d087/2014-Updates_on_the_web-based_VIOLIN_vaccine_database_and_analysis_system..pdf.pdf', event);\">\n    Updates on the web-based VIOLIN vaccine database and analysis system.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  He,  Y.; Racz,  R.; Sayers,  S.; Lin,  Y.; Todd,  T.; Hur,  J.; Li,  X.; Patel,  M.; <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Chung,  M.; Ostrow,  J.; Sylora,  A.; Dungarani,  P.; Ulysse,  G.; Kochhar,  K.; Vidri,  B.; Strait,  K.; Jourdian,  G., W.;  and Xiang,  Z.\n</span>\n\n  \n\n</span>\n\n  <i>Nucleic acids research</i>, 42(1): D1124-32. 1 2014.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6b25c1e8-a4f7-8e1b-529e-7c227d53d087/2014-Updates_on_the_web-based_VIOLIN_vaccine_database_and_analysis_system..pdf.pdf\"\n     onclick=\"log_download('he-racz-sayers-lin-todd-hur-li-patel-etal-updatesonthewebbasedviolinvaccinedatabaseandanalysissystem-2014', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6b25c1e8-a4f7-8e1b-529e-7c227d53d087/2014-Updates_on_the_web-based_VIOLIN_vaccine_database_and_analysis_system..pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Updates on the web-based VIOLIN vaccine database and analysis system. [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/24259431\"\n     onclick=\"log_download('he-racz-sayers-lin-todd-hur-li-patel-etal-updatesonthewebbasedviolinvaccinedatabaseandanalysissystem-2014', 'http://www.ncbi.nlm.nih.gov/pubmed/24259431', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Updates on the web-based VIOLIN vaccine database and analysis system. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1093/nar/gkt1133\"\n     onclick=\"log_download('he-racz-sayers-lin-todd-hur-li-patel-etal-updatesonthewebbasedviolinvaccinedatabaseandanalysissystem-2014', 'http://doi.org/10.1093/nar/gkt1133', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/he-racz-sayers-lin-todd-hur-li-patel-etal-updatesonthewebbasedviolinvaccinedatabaseandanalysissystem-2014\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('he-racz-sayers-lin-todd-hur-li-patel-etal-updatesonthewebbasedviolinvaccinedatabaseandanalysissystem-2014')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Updates on the web-based VIOLIN vaccine database and analysis system.},\n type = {article},\n year = {2014},\n pages = {D1124-32},\n volume = {42},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/24259431},\n month = {1},\n day = {1},\n id = {03a23edb-5633-3c44-af14-a2e41fed35f1},\n created = {2014-03-06T08:30:02.000Z},\n accessed = {2014-01-22},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2017-03-25T18:28:36.677Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {He2014},\n private_publication = {false},\n abstract = {The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, &gt;10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 &#x27;virmugens&#x27;, a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.},\n bibtype = {article},\n author = {He, Yongqun and Racz, Rebecca and Sayers, Samantha and Lin, Yu and Todd, Thomas and Hur, Junguk and Li, Xinna and Patel, Mukti and Zhao, Boyang and Chung, Monica and Ostrow, Joseph and Sylora, Andrew and Dungarani, Priya and Ulysse, Guerlain and Kochhar, Kanika and Vidri, Boris and Strait, Kelsey and Jourdian, George W and Xiang, Zuoshuang},\n doi = {10.1093/nar/gkt1133},\n journal = {Nucleic acids research},\n number = {1}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhao-hemann-lauffenburger-intratumorheterogeneityaltersmosteffectivedrugsindesignedcombinations-2014\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7860a1ef-e4b6-9a47-4f4f-7088d41d8973/2014-Intratumor_heterogeneity_alters_most_effective_drugs_in_designed_combinations..pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-hemann-lauffenburger-intratumorheterogeneityaltersmosteffectivedrugsindesignedcombinations-2014', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7860a1ef-e4b6-9a47-4f4f-7088d41d8973/2014-Intratumor_heterogeneity_alters_most_effective_drugs_in_designed_combinations..pdf.pdf', event);\">\n    Intratumor heterogeneity alters most effective drugs in designed combinations.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Hemann,  M., T.;  and Lauffenburger,  D., A.\n</span>\n\n  \n\n</span>\n\n  <i>Proceedings of the National Academy of Sciences of the United States of America</i>, 111(29): 10773-8. 7 2014.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7860a1ef-e4b6-9a47-4f4f-7088d41d8973/2014-Intratumor_heterogeneity_alters_most_effective_drugs_in_designed_combinations..pdf.pdf\"\n     onclick=\"log_download('zhao-hemann-lauffenburger-intratumorheterogeneityaltersmosteffectivedrugsindesignedcombinations-2014', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7860a1ef-e4b6-9a47-4f4f-7088d41d8973/2014-Intratumor_heterogeneity_alters_most_effective_drugs_in_designed_combinations..pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Intratumor heterogeneity alters most effective drugs in designed combinations. [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25002493,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4115561&amp;tool=pmcentrez&amp;rendertype=abstract\"\n     onclick=\"log_download('zhao-hemann-lauffenburger-intratumorheterogeneityaltersmosteffectivedrugsindesignedcombinations-2014', 'http://www.ncbi.nlm.nih.gov/pubmed/25002493,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4115561&amp;tool=pmcentrez&amp;rendertype=abstract', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Intratumor heterogeneity alters most effective drugs in designed combinations. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1073/pnas.1323934111\"\n     onclick=\"log_download('zhao-hemann-lauffenburger-intratumorheterogeneityaltersmosteffectivedrugsindesignedcombinations-2014', 'http://doi.org/10.1073/pnas.1323934111', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-hemann-lauffenburger-intratumorheterogeneityaltersmosteffectivedrugsindesignedcombinations-2014\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-hemann-lauffenburger-intratumorheterogeneityaltersmosteffectivedrugsindesignedcombinations-2014')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Intratumor heterogeneity alters most effective drugs in designed combinations.},\n type = {article},\n year = {2014},\n pages = {10773-8},\n volume = {111},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/25002493,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4115561&amp;tool=pmcentrez&amp;rendertype=abstract},\n month = {7},\n day = {22},\n id = {8eaa7f79-33fa-32db-b9fe-cd246ddc3e3b},\n created = {2014-08-03T05:54:23.000Z},\n accessed = {2014-08-18},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2017-03-25T18:28:36.677Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Zhao2014},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n abstract = {The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.},\n bibtype = {article},\n author = {Zhao, Boyang and Hemann, Michael T and Lauffenburger, Douglas A},\n doi = {10.1073/pnas.1323934111},\n journal = {Proceedings of the National Academy of Sciences of the United States of America},\n number = {29},\n keywords = {drug combination,drug optimization}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhao-pritchard-lauffenburger-hemann-addressinggenetictumorheterogeneitythroughcomputationallypredictivecombinationtherapy-2014\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/24318931\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-pritchard-lauffenburger-hemann-addressinggenetictumorheterogeneitythroughcomputationallypredictivecombinationtherapy-2014', 'http://www.ncbi.nlm.nih.gov/pubmed/24318931', event);\">\n    Addressing genetic tumor heterogeneity through computationally predictive combination therapy.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Pritchard,  J., R.; Lauffenburger,  D., A.;  and Hemann,  M., T.\n</span>\n\n  \n\n</span>\n\n  <i>Cancer discovery</i>, 4(2): 166-74. 2 2014.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/24318931\"\n     onclick=\"log_download('zhao-pritchard-lauffenburger-hemann-addressinggenetictumorheterogeneitythroughcomputationallypredictivecombinationtherapy-2014', 'http://www.ncbi.nlm.nih.gov/pubmed/24318931', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Addressing genetic tumor heterogeneity through computationally predictive combination therapy. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1158/2159-8290.CD-13-0465\"\n     onclick=\"log_download('zhao-pritchard-lauffenburger-hemann-addressinggenetictumorheterogeneitythroughcomputationallypredictivecombinationtherapy-2014', 'http://doi.org/10.1158/2159-8290.CD-13-0465', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-pritchard-lauffenburger-hemann-addressinggenetictumorheterogeneitythroughcomputationallypredictivecombinationtherapy-2014\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-pritchard-lauffenburger-hemann-addressinggenetictumorheterogeneitythroughcomputationallypredictivecombinationtherapy-2014')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Addressing genetic tumor heterogeneity through computationally predictive combination therapy.},\n type = {article},\n year = {2014},\n pages = {166-74},\n volume = {4},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/24318931},\n month = {2},\n day = {21},\n id = {6c5074a4-d224-32d0-acba-ca3697dfb01d},\n created = {2021-03-29T20:09:12.619Z},\n accessed = {2014-06-18},\n file_attached = {false},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2021-03-29T20:09:17.701Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Zhao2013},\n folder_uuids = {7e96e842-b029-41e6-a73f-7511890cd62e},\n private_publication = {false},\n abstract = {Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. We use RNA interference to model heterogeneous tumors, and demonstrate successful validation of computational predictions for how optimized drug combinations can yield superior effects on these tumors both in vitro and in vivo. Importantly, we discover here that for many such tumors knowledge of the predominant subpopulation is insufficient for determining the best drug combination. Surprisingly, in some cases, the optimal drug combination does not include drugs that would treat any particular subpopulation most effectively, challenging straightforward intuition. We confirm examples of such a case with survival studies in a murine preclinical lymphoma model. Altogether, our approach provides new insights about design principles for combination therapy in the context of intratumoral diversity, data that should inform the development of drug regimens superior for complex tumors. Significance: This study provides the first example of how combination drug regimens, using existing chemotherapies, can be rationally designed to maximize tumor cell death, while minimizing the outgrowth of clonal subpopulations.},\n bibtype = {article},\n author = {Zhao, Boyang and Pritchard, Justin R. and Lauffenburger, Douglas A. and Hemann, Michael T.},\n doi = {10.1158/2159-8290.CD-13-0465},\n journal = {Cancer discovery},\n number = {2},\n keywords = {drug combination,drug optimization,mathematical modeling,tumor heterogeneity}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. We use RNA interference to model heterogeneous tumors, and demonstrate successful validation of computational predictions for how optimized drug combinations can yield superior effects on these tumors both in vitro and in vivo. Importantly, we discover here that for many such tumors knowledge of the predominant subpopulation is insufficient for determining the best drug combination. Surprisingly, in some cases, the optimal drug combination does not include drugs that would treat any particular subpopulation most effectively, challenging straightforward intuition. We confirm examples of such a case with survival studies in a murine preclinical lymphoma model. Altogether, our approach provides new insights about design principles for combination therapy in the context of intratumoral diversity, data that should inform the development of drug regimens superior for complex tumors. Significance: This study provides the first example of how combination drug regimens, using existing chemotherapies, can be rationally designed to maximize tumor cell death, while minimizing the outgrowth of clonal subpopulations.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2012\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2012')\"\n      onkeypress=\"toggleGroup('group_2012')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2012</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"zhao-knepper-chou-pisitkun-largescalephosphotyrosineproteomicprofilingofratrenalcollectingductepitheliumrevealspredominanceofproteinsinvolvedincellpolaritydetermination-2012\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6ee512db-5429-ca21-25a7-43b3840f2dc3/2012-Large-scale_phosphotyrosine_proteomic_profiling_of_rat_renal_collecting_duct_epithelium_reveals_predominance_of_pro.pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-knepper-chou-pisitkun-largescalephosphotyrosineproteomicprofilingofratrenalcollectingductepitheliumrevealspredominanceofproteinsinvolvedincellpolaritydetermination-2012', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6ee512db-5429-ca21-25a7-43b3840f2dc3/2012-Large-scale_phosphotyrosine_proteomic_profiling_of_rat_renal_collecting_duct_epithelium_reveals_predominance_of_pro.pdf.pdf', event);\">\n    Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Knepper,  M., A.; Chou,  C.;  and Pisitkun,  T.\n</span>\n\n  \n\n</span>\n\n  <i>American journal of physiology. Cell physiology</i>, 302(1): C27-45. 1 2012.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6ee512db-5429-ca21-25a7-43b3840f2dc3/2012-Large-scale_phosphotyrosine_proteomic_profiling_of_rat_renal_collecting_duct_epithelium_reveals_predominance_of_pro.pdf.pdf\"\n     onclick=\"log_download('zhao-knepper-chou-pisitkun-largescalephosphotyrosineproteomicprofilingofratrenalcollectingductepitheliumrevealspredominanceofproteinsinvolvedincellpolaritydetermination-2012', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/6ee512db-5429-ca21-25a7-43b3840f2dc3/2012-Large-scale_phosphotyrosine_proteomic_profiling_of_rat_renal_collecting_duct_epithelium_reveals_predominance_of_pro.pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination. [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21940666\"\n     onclick=\"log_download('zhao-knepper-chou-pisitkun-largescalephosphotyrosineproteomicprofilingofratrenalcollectingductepitheliumrevealspredominanceofproteinsinvolvedincellpolaritydetermination-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/21940666', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1152/ajpcell.00300.2011\"\n     onclick=\"log_download('zhao-knepper-chou-pisitkun-largescalephosphotyrosineproteomicprofilingofratrenalcollectingductepitheliumrevealspredominanceofproteinsinvolvedincellpolaritydetermination-2012', 'http://doi.org/10.1152/ajpcell.00300.2011', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-knepper-chou-pisitkun-largescalephosphotyrosineproteomicprofilingofratrenalcollectingductepitheliumrevealspredominanceofproteinsinvolvedincellpolaritydetermination-2012\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-knepper-chou-pisitkun-largescalephosphotyrosineproteomicprofilingofratrenalcollectingductepitheliumrevealspredominanceofproteinsinvolvedincellpolaritydetermination-2012')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination.},\n type = {article},\n year = {2012},\n pages = {C27-45},\n volume = {302},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/21940666},\n month = {1},\n id = {7957de91-72c5-3dc3-a353-168f8c9396ea},\n created = {2012-01-15T21:40:01.000Z},\n accessed = {2012-01-10},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2017-03-25T18:28:36.677Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Zhao2012},\n private_publication = {false},\n abstract = {Although extensive phosphoproteomic information is available for renal epithelial cells, previous emphasis has been on phosphorylation of serines and threonines with little focus on tyrosine phosphorylation. Here we have carried out large-scale identification of phosphotyrosine sites in pervanadate-treated native inner medullary collecting ducts of rat, with a view towards identification of physiological processes in epithelial cells that are potentially regulated by tyrosine phosphorylation. The method combined antibody-based affinity purification of tyrosine phosphorylated peptides coupled with immobilized metal ion chromatography to enrich tyrosine phosphopeptides, which were identified by LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins were identified. A large fraction of these sites have not been previously reported on standard phosphoproteomic databases. All results are accessible via an online database: http://helixweb.nih.gov/ESBL/Database/iPY/. Analysis of surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP, DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation. These motifs plus contextual information, integrated using the NetworKIN tool, suggest that the protein tyrosine kinases involved include members of the insulin- and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms and KEGG pathways whose protein elements are overrepresented in our data set point to structures involved in epithelial cell-cell and cell-matrix interactions (&quot;adherens junction,&quot; &quot;tight junction,&quot; and &quot;focal adhesion&quot;) and to components of the actin cytoskeleton as major sites of tyrosine phosphorylation in these cells. In general, these findings mesh well with evidence that tyrosine phosphorylation plays a key role in epithelial polarity determination.},\n bibtype = {article},\n author = {Zhao, Boyang and Knepper, Mark A and Chou, Chung-Lin and Pisitkun, Trairak},\n doi = {10.1152/ajpcell.00300.2011},\n journal = {American journal of physiology. Cell physiology},\n number = {1}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Although extensive phosphoproteomic information is available for renal epithelial cells, previous emphasis has been on phosphorylation of serines and threonines with little focus on tyrosine phosphorylation. Here we have carried out large-scale identification of phosphotyrosine sites in pervanadate-treated native inner medullary collecting ducts of rat, with a view towards identification of physiological processes in epithelial cells that are potentially regulated by tyrosine phosphorylation. The method combined antibody-based affinity purification of tyrosine phosphorylated peptides coupled with immobilized metal ion chromatography to enrich tyrosine phosphopeptides, which were identified by LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins were identified. A large fraction of these sites have not been previously reported on standard phosphoproteomic databases. All results are accessible via an online database: http://helixweb.nih.gov/ESBL/Database/iPY/. Analysis of surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP, DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation. These motifs plus contextual information, integrated using the NetworKIN tool, suggest that the protein tyrosine kinases involved include members of the insulin- and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms and KEGG pathways whose protein elements are overrepresented in our data set point to structures involved in epithelial cell-cell and cell-matrix interactions (\"adherens junction,\" \"tight junction,\" and \"focal adhesion\") and to components of the actin cytoskeleton as major sites of tyrosine phosphorylation in these cells. In general, these findings mesh well with evidence that tyrosine phosphorylation plays a key role in epithelial polarity determination.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"zhao-pisitkun-hoffert-knepper-saeed-cphosaprogramtocalculateandvisualizeevolutionarilyconservedfunctionalphosphorylationsites-2012\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/11ae6f52-c251-69bb-04fd-820fdc30a339/2012-CPhos_A_program_to_calculate_and_visualize_evolutionarily_conserved_functional_phosphorylation_sites..pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-pisitkun-hoffert-knepper-saeed-cphosaprogramtocalculateandvisualizeevolutionarilyconservedfunctionalphosphorylationsites-2012', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/11ae6f52-c251-69bb-04fd-820fdc30a339/2012-CPhos_A_program_to_calculate_and_visualize_evolutionarily_conserved_functional_phosphorylation_sites..pdf.pdf', event);\">\n    CPhos: A program to calculate and visualize evolutionarily conserved functional phosphorylation sites.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Pisitkun,  T.; Hoffert,  J., D.; Knepper,  M., a.;  and Saeed,  F.\n</span>\n\n  \n\n</span>\n\n  <i>Proteomics</i>, 12(22): 3299-303. 11 2012.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/11ae6f52-c251-69bb-04fd-820fdc30a339/2012-CPhos_A_program_to_calculate_and_visualize_evolutionarily_conserved_functional_phosphorylation_sites..pdf.pdf\"\n     onclick=\"log_download('zhao-pisitkun-hoffert-knepper-saeed-cphosaprogramtocalculateandvisualizeevolutionarilyconservedfunctionalphosphorylationsites-2012', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/11ae6f52-c251-69bb-04fd-820fdc30a339/2012-CPhos_A_program_to_calculate_and_visualize_evolutionarily_conserved_functional_phosphorylation_sites..pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"CPhos: A program to calculate and visualize evolutionarily conserved functional phosphorylation sites. [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/23001821\"\n     onclick=\"log_download('zhao-pisitkun-hoffert-knepper-saeed-cphosaprogramtocalculateandvisualizeevolutionarilyconservedfunctionalphosphorylationsites-2012', 'http://www.ncbi.nlm.nih.gov/pubmed/23001821', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"CPhos: A program to calculate and visualize evolutionarily conserved functional phosphorylation sites. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/pmic.201200189\"\n     onclick=\"log_download('zhao-pisitkun-hoffert-knepper-saeed-cphosaprogramtocalculateandvisualizeevolutionarilyconservedfunctionalphosphorylationsites-2012', 'http://doi.org/10.1002/pmic.201200189', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-pisitkun-hoffert-knepper-saeed-cphosaprogramtocalculateandvisualizeevolutionarilyconservedfunctionalphosphorylationsites-2012\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-pisitkun-hoffert-knepper-saeed-cphosaprogramtocalculateandvisualizeevolutionarilyconservedfunctionalphosphorylationsites-2012')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {CPhos: A program to calculate and visualize evolutionarily conserved functional phosphorylation sites.},\n type = {article},\n year = {2012},\n keywords = {bioinformatics,conservation,functional significance,information theory,phos-},\n pages = {3299-303},\n volume = {12},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/23001821},\n month = {11},\n day = {24},\n id = {c67c6412-4c88-3f86-b148-2518ab2bea53},\n created = {2012-11-29T12:49:09.000Z},\n accessed = {2012-11-29},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2017-03-25T18:28:36.677Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Zhao2012a},\n private_publication = {false},\n abstract = {Profiling using high-throughput MS has discovered an overwhelming number of novel protein phosphorylation sites (&quot;phosphosites&quot;). However, the functional relevance of these sites is not always clear. In light of recent studies on the evolutionary mechanism of phosphorylation, we have developed CPhos, a Java program that can assess the conservation of phosphosites among species using an information theory-based approach. The degree of conservation established using CPhos can be used to assess the functional significance of phosphosites. CPhos has a user friendly graphical user interface and is available both as a web service and as a standalone Java application to assist phosphoproteomic researchers in analyzing and prioritizing lists of phosphosites for further experimental validation. CPhos can be accessed or downloaded at http://helixweb.nih.gov/CPhos/.},\n bibtype = {article},\n author = {Zhao, Boyang and Pisitkun, Trairak and Hoffert, Jason D and Knepper, Mark a and Saeed, Fahad},\n doi = {10.1002/pmic.201200189},\n journal = {Proteomics},\n number = {22}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Profiling using high-throughput MS has discovered an overwhelming number of novel protein phosphorylation sites (\"phosphosites\"). However, the functional relevance of these sites is not always clear. In light of recent studies on the evolutionary mechanism of phosphorylation, we have developed CPhos, a Java program that can assess the conservation of phosphosites among species using an information theory-based approach. The degree of conservation established using CPhos can be used to assess the functional significance of phosphosites. CPhos has a user friendly graphical user interface and is available both as a web service and as a standalone Java application to assist phosphoproteomic researchers in analyzing and prioritizing lists of phosphosites for further experimental validation. CPhos can be accessed or downloaded at http://helixweb.nih.gov/CPhos/.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2011\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2011')\"\n      onkeypress=\"toggleGroup('group_2011')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2011</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"zhao-obrien-kineticmechanismfortheexcisionofhypoxanthinebyescherichiacolialkaandevidenceforbindingtodnaends-2011\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7dc065ed-105f-7b57-7d5c-28b5328902e5/2011-Kinetic_mechanism_for_the_excision_of_hypoxanthine_by_Escherichia_coli_AlkA_and_evidence_for_binding_to_DNA_ends..pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'zhao-obrien-kineticmechanismfortheexcisionofhypoxanthinebyescherichiacolialkaandevidenceforbindingtodnaends-2011', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7dc065ed-105f-7b57-7d5c-28b5328902e5/2011-Kinetic_mechanism_for_the_excision_of_hypoxanthine_by_Escherichia_coli_AlkA_and_evidence_for_binding_to_DNA_ends..pdf.pdf', event);\">\n    Kinetic mechanism for the excision of hypoxanthine by Escherichia coli AlkA and evidence for binding to DNA ends.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>;  and O'Brien,  P., J.\n</span>\n\n  \n\n</span>\n\n  <i>Biochemistry</i>, 50(20): 4350-9. 5 2011.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7dc065ed-105f-7b57-7d5c-28b5328902e5/2011-Kinetic_mechanism_for_the_excision_of_hypoxanthine_by_Escherichia_coli_AlkA_and_evidence_for_binding_to_DNA_ends..pdf.pdf\"\n     onclick=\"log_download('zhao-obrien-kineticmechanismfortheexcisionofhypoxanthinebyescherichiacolialkaandevidenceforbindingtodnaends-2011', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/7dc065ed-105f-7b57-7d5c-28b5328902e5/2011-Kinetic_mechanism_for_the_excision_of_hypoxanthine_by_Escherichia_coli_AlkA_and_evidence_for_binding_to_DNA_ends..pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Kinetic mechanism for the excision of hypoxanthine by Escherichia coli AlkA and evidence for binding to DNA ends. [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/21491902,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3098123\"\n     onclick=\"log_download('zhao-obrien-kineticmechanismfortheexcisionofhypoxanthinebyescherichiacolialkaandevidenceforbindingtodnaends-2011', 'http://www.ncbi.nlm.nih.gov/pubmed/21491902,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3098123', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Kinetic mechanism for the excision of hypoxanthine by Escherichia coli AlkA and evidence for binding to DNA ends. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1021/bi200232c\"\n     onclick=\"log_download('zhao-obrien-kineticmechanismfortheexcisionofhypoxanthinebyescherichiacolialkaandevidenceforbindingtodnaends-2011', 'http://doi.org/10.1021/bi200232c', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/zhao-obrien-kineticmechanismfortheexcisionofhypoxanthinebyescherichiacolialkaandevidenceforbindingtodnaends-2011\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('zhao-obrien-kineticmechanismfortheexcisionofhypoxanthinebyescherichiacolialkaandevidenceforbindingtodnaends-2011')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Kinetic mechanism for the excision of hypoxanthine by Escherichia coli AlkA and evidence for binding to DNA ends.},\n type = {article},\n year = {2011},\n pages = {4350-9},\n volume = {50},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/21491902,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3098123},\n month = {5},\n day = {24},\n id = {2f72b967-3053-3dd8-924e-7d5f4f589512},\n created = {2011-05-22T00:54:50.000Z},\n accessed = {2011-04-16},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2021-03-28T17:21:31.527Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Zhao2011},\n private_publication = {false},\n abstract = {The Escherichia coli 3-methyladenine DNA glycosylase II protein (AlkA) recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair pathway. Although the enzyme was one of the first DNA repair glycosylases to be discovered more than 25 years ago and there are multiple crystal structures, the mechanism is poorly understood. Therefore, we have characterized the kinetic mechanism for the AlkA-catalyzed excision of the deaminated purine, hypoxanthine. The multiple-turnover glycosylase assays are consistent with Michaelis-Menten kinetics. However, under single-turnover conditions that are commonly employed for studying other DNA glycosylases, we observe an unusual biphasic protein saturation curve. Initially, the observed rate constant for excision increases with an increasing level of AlkA protein, but at higher protein concentrations, the rate constant decreases. This behavior can be most easily explained by tight binding to DNA ends and by crowding of multiple AlkA protamers on the DNA. Consistent with this model, crystal structures have shown the preferential binding of AlkA to DNA ends. By varying the position of the lesion, we identified an asymmetric substrate that does not show inhibition at higher concentrations of AlkA, and we performed pre-steady state and steady state kinetic analysis. Unlike the situation in other glycosylases, release of the abasic product is faster than N-glycosidic bond cleavage. Nevertheless, AlkA exhibits significant product inhibition under multiple-turnover conditions, and it binds approximately 10-fold more tightly to an abasic site than to a hypoxanthine lesion site. This tight binding could help protect abasic sites when the adaptive response to DNA alkylation is activated and very high levels of AlkA protein are present.},\n bibtype = {article},\n author = {Zhao, Boyang and O&#x27;Brien, Patrick John},\n doi = {10.1021/bi200232c},\n journal = {Biochemistry},\n number = {20}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The Escherichia coli 3-methyladenine DNA glycosylase II protein (AlkA) recognizes a broad range of oxidized and alkylated base lesions and catalyzes the hydrolysis of the N-glycosidic bond to initiate the base excision repair pathway. Although the enzyme was one of the first DNA repair glycosylases to be discovered more than 25 years ago and there are multiple crystal structures, the mechanism is poorly understood. Therefore, we have characterized the kinetic mechanism for the AlkA-catalyzed excision of the deaminated purine, hypoxanthine. The multiple-turnover glycosylase assays are consistent with Michaelis-Menten kinetics. However, under single-turnover conditions that are commonly employed for studying other DNA glycosylases, we observe an unusual biphasic protein saturation curve. Initially, the observed rate constant for excision increases with an increasing level of AlkA protein, but at higher protein concentrations, the rate constant decreases. This behavior can be most easily explained by tight binding to DNA ends and by crowding of multiple AlkA protamers on the DNA. Consistent with this model, crystal structures have shown the preferential binding of AlkA to DNA ends. By varying the position of the lesion, we identified an asymmetric substrate that does not show inhibition at higher concentrations of AlkA, and we performed pre-steady state and steady state kinetic analysis. Unlike the situation in other glycosylases, release of the abasic product is faster than N-glycosidic bond cleavage. Nevertheless, AlkA exhibits significant product inhibition under multiple-turnover conditions, and it binds approximately 10-fold more tightly to an abasic site than to a hypoxanthine lesion site. This tight binding could help protect abasic sites when the adaptive response to DNA alkylation is activated and very high levels of AlkA protein are present.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"feric-zhao-hoffert-pisitkun-knepper-largescalephosphoproteomicanalysisofmembraneproteinsinrenalproximalanddistaltubule-2011\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/47a0f115-d9a1-5609-3972-d12e9f347879/2011-Large-scale_phosphoproteomic_analysis_of_membrane_proteins_in_renal_proximal_and_distal_tubule..pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'feric-zhao-hoffert-pisitkun-knepper-largescalephosphoproteomicanalysisofmembraneproteinsinrenalproximalanddistaltubule-2011', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/47a0f115-d9a1-5609-3972-d12e9f347879/2011-Large-scale_phosphoproteomic_analysis_of_membrane_proteins_in_renal_proximal_and_distal_tubule..pdf.pdf', event);\">\n    Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Feric,  M.; <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Hoffert,  J., D.; Pisitkun,  T.;  and Knepper,  M., A.\n</span>\n\n  \n\n</span>\n\n  <i>American journal of physiology. Cell physiology</i>, 300(4): C755-70. 4 2011.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/47a0f115-d9a1-5609-3972-d12e9f347879/2011-Large-scale_phosphoproteomic_analysis_of_membrane_proteins_in_renal_proximal_and_distal_tubule..pdf.pdf\"\n     onclick=\"log_download('feric-zhao-hoffert-pisitkun-knepper-largescalephosphoproteomicanalysisofmembraneproteinsinrenalproximalanddistaltubule-2011', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/47a0f115-d9a1-5609-3972-d12e9f347879/2011-Large-scale_phosphoproteomic_analysis_of_membrane_proteins_in_renal_proximal_and_distal_tubule..pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule. [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3074622&amp;tool=pmcentrez&amp;rendertype=abstract\"\n     onclick=\"log_download('feric-zhao-hoffert-pisitkun-knepper-largescalephosphoproteomicanalysisofmembraneproteinsinrenalproximalanddistaltubule-2011', 'http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3074622&amp;tool=pmcentrez&amp;rendertype=abstract', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule. [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1152/ajpcell.00360.2010\"\n     onclick=\"log_download('feric-zhao-hoffert-pisitkun-knepper-largescalephosphoproteomicanalysisofmembraneproteinsinrenalproximalanddistaltubule-2011', 'http://doi.org/10.1152/ajpcell.00360.2010', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/feric-zhao-hoffert-pisitkun-knepper-largescalephosphoproteomicanalysisofmembraneproteinsinrenalproximalanddistaltubule-2011\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('feric-zhao-hoffert-pisitkun-knepper-largescalephosphoproteomicanalysisofmembraneproteinsinrenalproximalanddistaltubule-2011')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule.},\n type = {article},\n year = {2011},\n keywords = {Amino Acid Sequence,Animals,Chromatography,Distal,Distal: chemistry,Distal: cytology,Humans,Kidney Tubules,Liquid,Male,Membrane Proteins,Membrane Proteins: analysis,Membrane Proteins: genetics,Molecular Sequence Data,Phosphopeptides,Phosphopeptides: analysis,Phosphopeptides: genetics,Phosphoproteins,Phosphoproteins: analysis,Phosphoproteins: genetics,Protein Conformation,Protein Structure,Proteome,Proteome: analysis,Proximal,Proximal: chemistry,Proximal: cytology,Rats,Sequence Alignment,Sprague-Dawley,Tandem Mass Spectrometry,Tertiary},\n pages = {C755-70},\n volume = {300},\n websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3074622&amp;tool=pmcentrez&amp;rendertype=abstract},\n month = {4},\n id = {1473c45e-b556-3709-bde0-a19c51ec07ca},\n created = {2013-01-28T03:01:54.000Z},\n accessed = {2013-01-27},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2017-03-25T18:28:36.677Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Feric2011},\n private_publication = {false},\n abstract = {Recent advances in mass spectrometry (MS) have provided means for large-scale phosphoproteomic profiling of specific tissues. Here, we report results from large-scale tandem MS [liquid chromatography (LC)-MS/MS]-based phosphoproteomic profiling of biochemically isolated membranes from the renal cortex, with focus on transporters and regulatory proteins. Data sets were filtered (by target-decoy analysis) to limit false-positive identifications to &lt;2%. A total of 7,125 unique nonphosphorylated and 743 unique phosphorylated peptides were identified. Among the phosphopeptides identified were sites on transporter proteins, i.e., solute carrier (Slc, n = 63), ATP-binding cassette (Abc, n = 4), and aquaporin (Aqp, n = 3) family proteins. Database searches reveal that a majority of the phosphorylation sites identified in transporter proteins were previously unreported. Most of the Slc family proteins are apical or basolateral transporters expressed in proximal tubule cells, including proteins known to mediate transport of glucose, amino acids, organic ions, and inorganic ions. In addition, we identified potentially important phosphorylation sites for transport proteins from distal nephron segments, including the bumetanide-sensitive Na-K-2Cl cotransporter (Slc12a1 or NKCC2) at Ser(87), Thr(101), and Ser(126) and the thiazide-sensitive Na-Cl cotransporter (Slc12a3 or NCC) at Ser(71) and Ser(124). A subset of phosphorylation sites in regulatory proteins coincided with known functional motifs, suggesting specific regulatory roles. An online database from this study (http://dir.nhlbi.nih.gov/papers/lkem/rcmpd/) provides a resource for future studies of transporter regulation.},\n bibtype = {article},\n author = {Feric, Marina and Zhao, Boyang and Hoffert, Jason D and Pisitkun, Trairak and Knepper, Mark A},\n doi = {10.1152/ajpcell.00360.2010},\n journal = {American journal of physiology. Cell physiology},\n number = {4}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Recent advances in mass spectrometry (MS) have provided means for large-scale phosphoproteomic profiling of specific tissues. Here, we report results from large-scale tandem MS [liquid chromatography (LC)-MS/MS]-based phosphoproteomic profiling of biochemically isolated membranes from the renal cortex, with focus on transporters and regulatory proteins. Data sets were filtered (by target-decoy analysis) to limit false-positive identifications to <2%. A total of 7,125 unique nonphosphorylated and 743 unique phosphorylated peptides were identified. Among the phosphopeptides identified were sites on transporter proteins, i.e., solute carrier (Slc, n = 63), ATP-binding cassette (Abc, n = 4), and aquaporin (Aqp, n = 3) family proteins. Database searches reveal that a majority of the phosphorylation sites identified in transporter proteins were previously unreported. Most of the Slc family proteins are apical or basolateral transporters expressed in proximal tubule cells, including proteins known to mediate transport of glucose, amino acids, organic ions, and inorganic ions. In addition, we identified potentially important phosphorylation sites for transport proteins from distal nephron segments, including the bumetanide-sensitive Na-K-2Cl cotransporter (Slc12a1 or NKCC2) at Ser(87), Thr(101), and Ser(126) and the thiazide-sensitive Na-Cl cotransporter (Slc12a3 or NCC) at Ser(71) and Ser(124). A subset of phosphorylation sites in regulatory proteins coincided with known functional motifs, suggesting specific regulatory roles. An online database from this study (http://dir.nhlbi.nih.gov/papers/lkem/rcmpd/) provides a resource for future studies of transporter regulation.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2007\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2007')\"\n      onkeypress=\"toggleGroup('group_2007')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2007</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"xiang-todd-ku-kovacic-larson-chen-hodges-tian-etal-violinvaccineinvestigationandonlineinformationnetwork-2007\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/37e90530-b184-24f3-7ccd-4f3793d6230c/2007-VIOLIN_vaccine_investigation_and_online_information_network.pdf.pdf\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'xiang-todd-ku-kovacic-larson-chen-hodges-tian-etal-violinvaccineinvestigationandonlineinformationnetwork-2007', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/37e90530-b184-24f3-7ccd-4f3793d6230c/2007-VIOLIN_vaccine_investigation_and_online_information_network.pdf.pdf', event);\">\n    VIOLIN: vaccine investigation and online information network.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Xiang,  Z.; Todd,  T.; Ku,  K., P.; Kovacic,  B., L.; Larson,  C., B.; Chen,  F.; Hodges,  A., P.; Tian,  Y.; Olenzek,  E., A.; <a class=\"bibbase author link\" href=\"https://boyangzhao.github.io/publications/\">Zhao,  B.</a>; Colby,  L., A.; Rush,  H., G.; Gilsdorf,  J., R.; Jourdian,  G., W.;  and He,  Y.\n</span>\n\n  \n\n</span>\n\n  <i>Nucleic Acids Research</i>, 36(Database): D923-D928. 12 2007.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/37e90530-b184-24f3-7ccd-4f3793d6230c/2007-VIOLIN_vaccine_investigation_and_online_information_network.pdf.pdf\"\n     onclick=\"log_download('xiang-todd-ku-kovacic-larson-chen-hodges-tian-etal-violinvaccineinvestigationandonlineinformationnetwork-2007', 'https://bibbase.org/service/mendeley/3cf34896-6274-3001-ad57-9ba3f52c9235/file/37e90530-b184-24f3-7ccd-4f3793d6230c/2007-VIOLIN_vaccine_investigation_and_online_information_network.pdf.pdf', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/pdf.svg\"\n\t     alt=\"VIOLIN: vaccine investigation and online information network [pdf]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/18025042,https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm1039\"\n     onclick=\"log_download('xiang-todd-ku-kovacic-larson-chen-hodges-tian-etal-violinvaccineinvestigationandonlineinformationnetwork-2007', 'http://www.ncbi.nlm.nih.gov/pubmed/18025042,https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm1039', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"VIOLIN: vaccine investigation and online information network [link]\"\n       title=\"Website\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Website</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1093/nar/gkm1039\"\n     onclick=\"log_download('xiang-todd-ku-kovacic-larson-chen-hodges-tian-etal-violinvaccineinvestigationandonlineinformationnetwork-2007', 'http://doi.org/10.1093/nar/gkm1039', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/xiang-todd-ku-kovacic-larson-chen-hodges-tian-etal-violinvaccineinvestigationandonlineinformationnetwork-2007\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('xiang-todd-ku-kovacic-larson-chen-hodges-tian-etal-violinvaccineinvestigationandonlineinformationnetwork-2007')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{\n title = {VIOLIN: vaccine investigation and online information network},\n type = {article},\n year = {2007},\n keywords = {database},\n pages = {D923-D928},\n volume = {36},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/18025042,https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm1039},\n month = {12},\n day = {23},\n id = {ac4d6ece-2838-3f27-bb85-0d27f2ac0bf7},\n created = {2009-08-22T08:04:52.000Z},\n accessed = {2011-05-21},\n file_attached = {true},\n profile_id = {3cf34896-6274-3001-ad57-9ba3f52c9235},\n last_modified = {2018-02-17T12:57:12.685Z},\n read = {true},\n starred = {false},\n authored = {true},\n confirmed = {true},\n hidden = {false},\n citation_key = {Xiang2008},\n private_publication = {false},\n abstract = {Vaccines are among the most efficacious and cost-effective tools for reducing morbidity and mortality caused by infectious diseases. The vaccine investigation and online information network (VIOLIN) is a web-based central resource, allowing easy curation, comparison and analysis of vaccine-related research data across various human pathogens (e.g. Haemophilus influenzae, human immunodeficiency virus (HIV) and Plasmodium falciparum) of medical importance and across humans, other natural hosts and laboratory animals. Vaccine-related peer-reviewed literature data have been downloaded into the database from PubMed and are searchable through various literature search programs. Vaccine data are also annotated, edited and submitted to the database through a web-based interactive system that integrates efficient computational literature mining and accurate manual curation. Curated information includes general microbial pathogenesis and host protective immunity, vaccine preparation and characteristics, stimulated host responses after vaccination and protection efficacy after challenge. Vaccine-related pathogen and host genes are also annotated and available for searching through customized BLAST programs. All VIOLIN data are available for download in an eXtensible Markup Language (XML)-based data exchange format. VIOLIN is expected to become a centralized source of vaccine information and to provide investigators in basic and clinical sciences with curated data and bioinformatics tools for vaccine research and development. VIOLIN is publicly available at http://www.violinet.org.},\n bibtype = {article},\n author = {Xiang, Zuoshuang and Todd, Thomas and Ku, Kim P and Kovacic, Bethany L and Larson, Charles B and Chen, Fang and Hodges, Andrew P and Tian, Yuying and Olenzek, Elizabeth A and Zhao, Boyang and Colby, Lesley A and Rush, Howard G and Gilsdorf, Janet R and Jourdian, George W and He, Yongqun},\n doi = {10.1093/nar/gkm1039},\n journal = {Nucleic Acids Research},\n number = {Database}\n}</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Vaccines are among the most efficacious and cost-effective tools for reducing morbidity and mortality caused by infectious diseases. The vaccine investigation and online information network (VIOLIN) is a web-based central resource, allowing easy curation, comparison and analysis of vaccine-related research data across various human pathogens (e.g. Haemophilus influenzae, human immunodeficiency virus (HIV) and Plasmodium falciparum) of medical importance and across humans, other natural hosts and laboratory animals. Vaccine-related peer-reviewed literature data have been downloaded into the database from PubMed and are searchable through various literature search programs. Vaccine data are also annotated, edited and submitted to the database through a web-based interactive system that integrates efficient computational literature mining and accurate manual curation. Curated information includes general microbial pathogenesis and host protective immunity, vaccine preparation and characteristics, stimulated host responses after vaccination and protection efficacy after challenge. Vaccine-related pathogen and host genes are also annotated and available for searching through customized BLAST programs. All VIOLIN data are available for download in an eXtensible Markup Language (XML)-based data exchange format. VIOLIN is expected to become a centralized source of vaccine information and to provide investigators in basic and clinical sciences with curated data and bioinformatics tools for vaccine research and development. VIOLIN is publicly available at http://www.violinet.org.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n\n\n\n  </div>\n\n\n  <!-- Modal -->\n\n  <!-- <iframe id=\"bibbase_network_frame\" -->\n  <!--         src=\"//bibbase.org/network/control\" -->\n  <!--         style=\"display: none;\"> -->\n  <!-- </iframe> -->\n\n</div>\n"}; document.write(bibbase_data.data);