ArticlePLoS genetics2016
Reverse Chemical Genetics: Comprehensive Fitness Profiling Reveals the Spectrum of Drug Target Interactions.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- From Oak to Wine: Evolution, Admixture, and Adaptation of California and British Columbia Saccharomyces Cerevisiae Wine Strains.Genome biology and evolution · 2026Article
- JAK2/STAT3-dependent regulation of MDM4/MDM2-p53 signaling in methotrexate-induced ferroptosis and nephrotoxicity.Archives of pharmacal research · 2026Article
- Deep mutational scanning of Pneumocystis jirovecii dihydrofolate reductase reveals allosteric mechanism of resistance to an antifolate.PLoS genetics · 2024Article
- Current trends and future prospects of drug repositioning in gastrointestinal oncology.Frontiers in pharmacology · 2023Review
- Advances in fungal chemical genomics for the discovery of new antifungal agents.Annals of the New York Academy of Sciences · 2021Review
- Overcoming cancer therapeutic bottleneck by drug repurposing.Signal transduction and targeted therapy · 2020Review
- How Surrogate and Chemical Genetics in Model Organisms Can Suggest Therapies for Human Genetic Diseases.Genetics · 2018Review
- Genome-Wide Screen RevealsG3 (Bethesda, Md.) · 2017Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The emergence and prevalence of drug resistance demands streamlined strategies to identify drug resistant variants in a fast, systematic and cost-effective way. Methods commonly used to understand and predict drug resistance rely on limited clinical studies from patients who are refractory to drugs or on laborious evolution experiments with poor coverage of the gene variants. Here, we report an integrative functional variomics methodology combining deep sequencing and a Bayesian statistical model to provide a comprehensive list of drug resistance alleles from complex variant populations. Dihydrofolate reductase, the target of methotrexate chemotherapy drug, was used as a model to identify functional mutant alleles correlated with methotrexate resistance. This systematic approach identified previously reported resistance mutations, as well as novel point mutations that were validated in vivo. Use of this systematic strategy as a routine diagnostics tool widens the scope of successful drug research and development.
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Registered trials
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