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A genome scale overexpression screen to reveal drug activity in human cells Arnoldo, Anthony; Kittanakom, Saranya; Heisler, Lawrence E; Mak, Anthony B; Shukalyuk, Andrey I; Torti, Dax; Moffat, Jason; Giaever, Guri; Nislow, Corey

Abstract

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.

Item Metadata

Title
A genome scale overexpression screen to reveal drug activity in human cells
Creator
Arnoldo, Anthony; Kittanakom, Saranya; Heisler, Lawrence E; Mak, Anthony B; Shukalyuk, Andrey I; Torti, Dax; Moffat, Jason; Giaever, Guri; Nislow, Corey
Publisher
BioMed Central
Date Issued
2014-04-29
Description
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.
Genre
Article
Type
Text
Language
eng
Date Available
2016-01-21
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0223617
URI
http://hdl.handle.net/2429/56670
Affiliation
Pharmaceutical Sciences, Faculty of; Non UBC
Citation
Genome Medicine. 2014 Apr 29;6(4):32
Publisher DOI
10.1186/gm549
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Arnoldo et al.; licensee BioMed Central Ltd.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Rights

Attribution 4.0 International (CC BY 4.0)