Multi-omics "upstream analysis" of regulatory genomic regions helps identifying targets against methotrexate resistance of colon cancer.

Abstract

We present an "upstream analysis" strategy for causal analysis of multiple "-omics" data. It analyzes promoters using the TRANSFAC database, combines it with an analysis of the upstream signal transduction pathways and identifies master regulators as potential drug targets for a pathological process. We applied this approach to a complex multi-omics data set that contains transcriptomics, proteomics and epigenomics data. We identified the following potential drug targets against induced resistance of cancer cells towards chemotherapy by methotrexate (MTX): TGFalpha, IGFBP7, alpha9-integrin, and the following chemical compounds: zardaverine and divalproex as well as human metabolites such as nicotinamide N-oxide.

• Authors: Alexander E Kel, Philip Stegmaier, Tagir Valeev, Jeannette Koschmann, Vladimir Poroikov, Olga V Kel-Margoulis, Edgar Wingender
• Journal: EuPA open proteomics (EuPA Open Proteom) Vol. 13 Pg. 1-13 (Dec 2016) ISSN: 2212-9685 [Electronic] Netherlands
• PMID: 29900117 (Publication Type: Journal Article)