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• W2095442568 abstract "•Drug and target discovery will benefit from cell line genomic characterization. •Quality cell models and selective small molecules are critical tools for success. •The cancer field has used this approach, but other diseases would also benefit. Over the past decade, tremendous progress in high-throughput small molecule-screening methods has facilitated the rapid expansion of phenotype-based data. Parallel advances in genomic characterization methods have complemented these efforts by providing a growing list of annotated cell line features. Together, these developments have paved the way for feature-based identification of novel, exploitable cellular dependencies, subsequently expanding our therapeutic toolkit in cancer and other diseases. Here, we provide an overview of the evolution of phenotypic small-molecule profiling and discuss the most significant and recent profiling and analytical efforts, their impact on the field, and their clinical ramifications. We additionally provide a perspective for future developments in phenotypic profiling efforts guided by genomic science. Over the past decade, tremendous progress in high-throughput small molecule-screening methods has facilitated the rapid expansion of phenotype-based data. Parallel advances in genomic characterization methods have complemented these efforts by providing a growing list of annotated cell line features. Together, these developments have paved the way for feature-based identification of novel, exploitable cellular dependencies, subsequently expanding our therapeutic toolkit in cancer and other diseases. Here, we provide an overview of the evolution of phenotypic small-molecule profiling and discuss the most significant and recent profiling and analytical efforts, their impact on the field, and their clinical ramifications. We additionally provide a perspective for future developments in phenotypic profiling efforts guided by genomic science. small molecule perturbagens with previously known and annotated mechanism(s) of action a project led by the Broad Institute, the Novartis Institute for Biomedical Research, and the Genomics Institute of the Novartis Research Foundation, focused on the genomic and pharmacologic characterization of a set of approximately 1000 human cancer cell lines (http://www.broadinstitute.org/ccle/home). pathway or process on which a particular cell type or cell state depends for survival. measurement of the protein(s) to which a small molecule binds, directly or indirectly. a computational method to determine the enrichment of a defined set of genes in the gene-expression analysis of two biological states. The collection of gene sets under consideration can be derived experimentally, computationally, or by biological function. a graph-theoretic construct that expresses relations between proteins based on evidence of interaction between them (may be physical interaction, coregulation, or combinations of evidence). the identification of novel chemical matter with similar biological function, but different structure, to that of a starting small molecule. peripheral B lymphocytes transformed by EBV, these cells are often useful as a source of DNA and cells from individuals for biological characterization. mathematical technique allowing connection of two variables via a third shared variable that connects to each one. an analysis technique that merges data from separate studies of the same subject(s) into a single analysis. direct measurement of the levels of small-molecule metabolites in a cellular system under various conditions. a program operated by the National Institutes of Health focused on the discovery of novel chemical probes of biological processes and disease states (http://mli.nih.gov/mli/mlp-overview/) mathematical technique that combines information from multiple predictive variables to estimate the value of a predicted variable. a long-standing project operated by the National Cancer Institute involving the screening of a collection of 60 cancer cell lines for growth inhibition after treatment with small molecules of interest (http://dtp.nci.nih.gov/branches/btb/ivclsp.html). using performance of small molecules across multiple assays or using multiple features as a measure of their similarity (instead of, for example, chemical structure similarity). a quantitative measurement of phenotype spanning multiple variables, such as gene-expression in response to compound treatment. a genetic determinant of a quantitative trait of an organism, such as size. specific set of multiple features reporting on a disease state or action of a perturbagen. unbiased measurement of multiple cellular features reporting on small-molecule action. unbiased measurement of multiple gene-expression features (usually as transcripts, possibly genome wide)." @default.
• W2095442568 created "2016-06-24" @default.
• W2095442568 creator A5021915671 @default.
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• W2095442568 date "2015-01-01" @default.
• W2095442568 modified "2023-10-18" @default.
• W2095442568 title "Integrating phenotypic small-molecule profiling and human genetics: the next phase in drug discovery" @default.
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• W2095442568 doi "https://doi.org/10.1016/j.tig.2014.11.002" @default.
• W2095442568 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4281276" @default.
• W2095442568 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25498789" @default.
• W2095442568 hasPublicationYear "2015" @default.
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