An integrated network platform for contextual prioritization of drugs and pathways

Molecular BioSystems
Aldo Segura-CabreraKakajan Komurov

Abstract

Repurposing of drugs to novel disease indications has promise for faster clinical translation. However, identifying the best drugs for a given pathological context is not trivial. We developed an integrated random walk-based network framework that combines functional biomolecular relationships and known drug-target interactions as a platform for contextual prioritization of drugs, genes and pathways. We show that the use of gene-centric or drug-centric data, such as gene expression data or a phenotypic drug screen, respectively, within this network platform can effectively prioritize drugs and pathways, respectively, to the studied biological context. We demonstrate that various genomic data can be used as contextual cues to effectively prioritize drugs to the studied context, while similarly, phenotypic drug screen data can be used to effectively prioritize genes and pathways to the studied phenotypic context. As a proof-of-principle, we showcase the use of our platform to identify known and novel drug indications against different subsets of breast cancers through contextual prioritization based on genome-wide gene expression, shRNA and drug screen and clinical survival data. The integrated network and associated methods are ...Continue Reading

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Citations

Mar 23, 2017·Scientific Reports·Aldo Segura-CabreraKakajan Komurov
Jul 31, 2018·Expert Opinion on Drug Discovery·Theodora Katsila, Minos-Timotheos Matsoukas
Nov 28, 2019·Journal of Biomolecular Structure & Dynamics·Shivalika PathaniaManoj Kumar
Jan 6, 2017·Oxidative Medicine and Cellular Longevity·Yuhei Nishimura, Hideaki Hara
Aug 10, 2020·Scientific Reports·Ki-Jo KimIlias Tagkopoulos
May 13, 2020·Briefings in Bioinformatics·Chun-Chun WangXing Chen

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