A genome scale overexpression screen to reveal drug activity in human cells

Target identification is a critical step in the lengthy and expensive process of drug development. Here, we describe a genome-wide screening platform that uses systematic overexpression of pooled human ORFs to understand drug mode-of-action and resistance mechanisms. We first calibrated our screen w...

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Bibliographic Details
Published in:	Genome medicine 2014-04, Vol.6 (4), p.32-32
Main Authors:	Arnoldo, Anthony, Kittanakom, Saranya, Heisler, Lawrence E, Mak, Anthony B, Shukalyuk, Andrey I, Torti, Dax, Moffat, Jason, Giaever, Guri, Nislow, Corey
Format:	Article
Language:	eng
Subjects:	Cells Drugs Genes Genetic transcription Genomes Genomics Method
Online Access:	Get full text
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Summary:	Target identification is a critical step in the lengthy and expensive process of drug development. Here, we describe a genome-wide screening platform that uses systematic overexpression of pooled human ORFs to understand drug mode-of-action and resistance mechanisms. We first calibrated our screen with the well-characterized drug methotrexate. We then identified new genes involved in the bioactivity of diverse drugs including antineoplastic agents and biologically active molecules. Finally, we focused on the transcription factor RHOXF2 whose overexpression conferred resistance to DNA damaging agents. This approach represents an orthogonal method for functional screening and, to our knowledge, has never been reported before.
ISSN:	1756-994X 1756-994X