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

EuPA Open Proteom. 2016 Sep 9:13:1-13. doi: 10.1016/j.euprot.2016.09.002. eCollection 2016 Dec.

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.

Keywords: ChIP-seq; Microarray data; Pathway analysis; Promoter analysis; Proteomics data; Upstream analysis.