title: Integrating phenotypic small-molecule profiling and human genetics: the next phase in drug discovery.
abstract: 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.
authors.affiliation: Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Johannessen
authors.affiliation: Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Clemons
authors.affiliation: Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. Electronic address: bwagner@broadinstitute.org.
authors.forename: Bridget K
authors.initials: BK
authors.lastname: Wagner
mesh_terms: D055808:Drug Discovery; D004351:Drug Resistance / Q000235:genetics; D005826:Genetics, Medical; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D010641:Phenotype; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D054852:Small Molecule Libraries
keywords: cell line profiling; genotype–phenotype; small molecule