Correlating chemical sensitivity and basal gene expression reveals mechanism of action

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Correlating chemical sensitivity and basal gene expression reveals mechanism of action

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Title: Correlating chemical sensitivity and basal gene expression reveals mechanism of action
Author: Rees, Matthew G; Seashore-Ludlow, Brinton; Cheah, Jaime H; Adams, Drew J; Price, Edmund V; Gill, Shubhroz; Javaid, Sarah; Coletti, Matthew E; Jones, Victor Victor; Bodycombe, Nicole E; Soule, Christian K; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Kotz, Joanne D; Hon, C Suk-Yee; Munoz, Benito; Liefeld, Ted; Dancík, Vlado; Haber, Daniel A; Clish, Clary B; Bittker, Joshua A; Palmer, Michelle; Wagner, Bridget K; Clemons, Paul A; Shamji, Alykhan Farid; Schreiber, Stuart L.

Note: Order does not necessarily reflect citation order of authors.

Citation: Rees, Matthew G, Brinton Seashore-Ludlow, Jaime H Cheah, Drew J Adams, Edmund V Price, Shubhroz Gill, Sarah Javaid, et al. 2015. “Correlating Chemical Sensitivity and Basal Gene Expression Reveals Mechanism of Action.” Nature Chemical Biology 12 (2) (December 14): 109–116. doi:10.1038/nchembio.1986.
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Abstract: Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown. To test this idea, we correlated the sensitivity patterns of 481 compounds with ~19,000 basal transcript levels across 823 different human cancer cell lines and identified selective outlier transcripts. This process yielded many novel mechanistic insights, including the identification of activation mechanisms, cellular transporters, and direct protein targets. We found that ML239, originally identified in a phenotypic screen for selective cytotoxicity in breast cancer stem-like cells, most likely acts through activation of fatty acid desaturase 2 (FADS2). These data and analytical tools are available to the research community through the Cancer Therapeutics Response Portal.
Published Version: 10.1038/nchembio.1986
Other Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718762/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33464171
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