ArticleNature chemical biology2016
Correlating chemical sensitivity and basal gene expression reveals mechanism of action.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 584 papers, 1 of them a synthesis that pooled it.
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Who cites it
584 citing papers in PubMed, 1 synthesis or guideline pooled it, 969 citations in OpenAlex.
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- Functional genomics and proteomics identify Folate Carrier SLC19A1 as a predictor of pralatrexate sensitivity in diverse T-cell lymphoma models.Molecular cancer therapeutics · 2026Article
524 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.