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

Q4 Biochemistry, Genetics and Molecular Biology
Alexander E. Kel , Philip Stegmaier , Tagir Valeev , Jeannette Koschmann , Vladimir Poroikov , Olga V. Kel-Margoulis , Edgar Wingender
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引用次数: 37

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.

Abstract Image

调控基因组区域的多组学“上游分析”有助于确定结肠癌抗甲氨蝶呤耐药的靶标
我们提出了一种“上游分析”策略,用于对多个“组学”数据进行因果分析。它使用TRANSFAC数据库分析启动子,将其与上游信号转导途径的分析相结合,并确定主调控因子作为病理过程的潜在药物靶点。我们将这种方法应用于包含转录组学、蛋白质组学和表观基因组学数据的复杂多组学数据集。我们确定了以下潜在的药物靶点,以对抗甲氨蝶呤(MTX)诱导的癌细胞对化疗的耐药:TGFalpha, IGFBP7, alpha9整合素,以及以下化合物:扎达弗林和双丙戊酸以及人类代谢物如烟酰胺n -氧化物。
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来源期刊
EuPA Open Proteomics
EuPA Open Proteomics Biochemistry, Genetics and Molecular Biology-Biochemistry
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