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

作者：Alexander E Kel, Philip Stegmaier, Tagir Valeev, Jeannette Koschmann, Vladimir Poroikov, Olga V Kel-Margoulis, Edgar Wingender · 发表于：EuPA Open Proteomics · 年份：2016 · DOI：10.1016/j.euprot.2016.09.002 · 被引用次数：44 · 研究领域：RNA modifications and cancer、Genomics and Chromatin Dynamics、Cancer Genomics and Diagnostics

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.