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

作者:Arnoldo Anthony; Kittanakom Saranya; Heisler Lawrence E; Mak Anthony B; Shukalyuk Andrey I; Torti Dax; Moffat Jason; Giaever Guri; Nislow Corey*
来源:Genome Medicine, 2014, 6(4): 32.
DOI:10.1186/gm549

摘要

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.

  • 出版日期2014-4-29