Morphology and gene expression profiling provide complementary information for mapping cell state

Morphology and gene expression profiling provide complementary information for mapping cell state. Way, G. P., Natoli, T., Adeboye, A., Litichevskiy, L., Yang, A., Lu, X., Caicedo, J. C., Cimini, B. A., Karhohs, K., Logan, D. J., Rohban, M. H., Kost-Alimova, M., Hartland, K., Bornholdt, M., Chandrasekaran, S. N., Haghighi, M., Weisbart, E., Singh, S., Subramanian, A., & Carpenter, A. E. Cell Systems, 13(11):911–923.e9, November, 2022.

Paper doi abstract bibtex

Morphological and gene expression proﬁling can cost-effectively capture thousands of features in thousands of samples across perturbations by disease, mutation, or drug treatments, but it is unclear to what extent the two modalities capture overlapping versus complementary information. Here, using both the L1000 and Cell Painting assays to proﬁle gene expression and cell morphology, respectively, we perturb human A549 lung cancer cells with 1,327 small molecules from the Drug Repurposing Hub across six doses, providing a data resource including dose-response data from both assays. The two assays capture both shared and complementary information for mapping cell state. Cell Painting proﬁles from compound perturbations are more reproducible and show more diversity but measure fewer distinct groups of features. Applying unsupervised and supervised methods to predict compound mechanisms of action (MOAs) and gene targets, we ﬁnd that the two assays not only provide a partially shared but also a complementary view of drug mechanisms. Given the numerous applications of proﬁling in biology, our analyses provide guidance for planning experiments that proﬁle cells for detecting distinct cell types, disease phenotypes, and response to chemical or genetic perturbations.

@article{way_morphology_2022,
	title = {Morphology and gene expression profiling provide complementary information for mapping cell state},
	volume = {13},
	issn = {24054712},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S2405471222004021},
	doi = {10.1016/j.cels.2022.10.001},
	abstract = {Morphological and gene expression proﬁling can cost-effectively capture thousands of features in thousands of samples across perturbations by disease, mutation, or drug treatments, but it is unclear to what extent the two modalities capture overlapping versus complementary information. Here, using both the L1000 and Cell Painting assays to proﬁle gene expression and cell morphology, respectively, we perturb human A549 lung cancer cells with 1,327 small molecules from the Drug Repurposing Hub across six doses, providing a data resource including dose-response data from both assays. The two assays capture both shared and complementary information for mapping cell state. Cell Painting proﬁles from compound perturbations are more reproducible and show more diversity but measure fewer distinct groups of features. Applying unsupervised and supervised methods to predict compound mechanisms of action (MOAs) and gene targets, we ﬁnd that the two assays not only provide a partially shared but also a complementary view of drug mechanisms. Given the numerous applications of proﬁling in biology, our analyses provide guidance for planning experiments that proﬁle cells for detecting distinct cell types, disease phenotypes, and response to chemical or genetic perturbations.},
	language = {en},
	number = {11},
	urldate = {2023-12-06},
	journal = {Cell Systems},
	author = {Way, Gregory P. and Natoli, Ted and Adeboye, Adeniyi and Litichevskiy, Lev and Yang, Andrew and Lu, Xiaodong and Caicedo, Juan C. and Cimini, Beth A. and Karhohs, Kyle and Logan, David J. and Rohban, Mohammad H. and Kost-Alimova, Maria and Hartland, Kate and Bornholdt, Michael and Chandrasekaran, Srinivas Niranj and Haghighi, Marzieh and Weisbart, Erin and Singh, Shantanu and Subramanian, Aravind and Carpenter, Anne E.},
	month = nov,
	year = {2022},
	pages = {911--923.e9},
	file = {Way et al. - 2022 - Morphology and gene expression profiling provide c.pdf:/Users/flodje_uds/Zotero/storage/NBHY2WBG/Way et al. - 2022 - Morphology and gene expression profiling provide c.pdf:application/pdf},
}

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