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

•Upstream analysis strategy for multi-omics data is proposed.•Drug targets are predicted by search for TFBS and analysis of signaling network.•Methotrexate resistance data include transcriptomics, proteomics and epigenomics.•Predicted targets are: TGFalpha, IGFBP7, alpha9-integrin.•Predicted drugs are: zardaverine, divalproex and human metabolite nicotinamide N-oxide.

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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide