SigFuge: single gene clustering of RNA-seq reveals differential isoform usage among cancer samples. Kimes, P. K, Cabanski, C. R, Wilkerson, M. D, Zhao, N., Johnson, A. R, Perou, C. M, Makowski, L., Maher, C. a, Liu, Y., Marron, J S, Hayes, D N., a. Maher, C., Liu, Y., Marron, J S, & Hayes, D N. Nucleic acids research, 42(14):1--12, 2014.
SigFuge: single gene clustering of RNA-seq reveals differential isoform usage among cancer samples. [link]Paper  doi  abstract   bibtex   
High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A, a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attention to known sample stratifications, SigFuge offers a novel approach to unsupervised screening of genetic loci across RNA-seq cohorts. SigFuge is available as an R package through Bioconductor.
@article{kimes_sigfuge:_2014,
	title = {{SigFuge}: single gene clustering of {RNA}-seq reveals differential isoform usage among cancer samples.},
	volume = {42},
	issn = {1362-4962},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25030904},
	doi = {10.1093/nar/gku521},
	abstract = {High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A, a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attention to known sample stratifications, SigFuge offers a novel approach to unsupervised screening of genetic loci across RNA-seq cohorts. SigFuge is available as an R package through Bioconductor.},
	number = {14},
	journal = {Nucleic acids research},
	author = {Kimes, Patrick K and Cabanski, Christopher R and Wilkerson, Matthew D and Zhao, Ni and Johnson, Amy R and Perou, Charles M and Makowski, Liza and Maher, Christopher a and Liu, Yufeng and Marron, J S and Hayes, D Neil and a. Maher, Christopher and Liu, Yufeng and Marron, J S and Hayes, D Neil},
	year = {2014},
	pmid = {25030904},
	pages = {1--12}
}
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