Prioritizing therapeutics for lung cancer: an integrative meta-analysis of cancer gene signatures and chemogenomic data

PLoS Computational Biology
Kristen FortneyIgor Jurisica

Abstract

Repurposing FDA-approved drugs with the aid of gene signatures of disease can accelerate the development of new therapeutics. A major challenge to developing reliable drug predictions is heterogeneity. Different gene signatures of the same disease or drug treatment often show poor overlap across studies, as a consequence of both biological and technical variability, and this can affect the quality and reproducibility of computational drug predictions. Existing algorithms for signature-based drug repurposing use only individual signatures as input. But for many diseases, there are dozens of signatures in the public domain. Methods that exploit all available transcriptional knowledge on a disease should produce improved drug predictions. Here, we adapt an established meta-analysis framework to address the problem of drug repurposing using an ensemble of disease signatures. Our computational pipeline takes as input a collection of disease signatures, and outputs a list of drugs predicted to consistently reverse pathological gene changes. We apply our method to conduct the largest and most systematic repurposing study on lung cancer transcriptomes, using 21 signatures. We show that scaling up transcriptional knowledge significantly...Continue Reading

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Citations

Jan 11, 2017·Briefings in Bioinformatics·Aliyu MusaFrank Emmert-Streib
Dec 19, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Laura B FergusonR Dayne Mayfield
Mar 22, 2019·The Cancer Journal·Karel K M KoudijsHenk-Jan Guchelaar
Apr 14, 2018·BMC Cancer·Claire Jean-QuartierAndreas Holzinger
Oct 17, 2017·Frontiers in Physiology·Tingting ZhengGianni Panagiotou
Nov 14, 2019·International Journal of Molecular Sciences·Yurong GaoJaemin Lee
Feb 6, 2018·World Journal of Hepatology·Venkat BhatMamatha Bhat
Oct 17, 2019·Seminars in Cancer Biology·Vikram ShawSanjay K Srivastava
Nov 8, 2019·Seminars in Cancer Biology·Ramanathan KaruppasamyDaisuke Kihara
May 3, 2021·CPT: Pharmacometrics & Systems Pharmacology·Rachel A HodosPaul B McCray

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Software Mentioned

NAViGaTOR
Connectivity Map ( CMap )
Connectivity
TOP
hgu133a
R
PubChem Chemical Structure Clustering Tool
igraph
Bioconductor
CMapBatch

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