Aug 20, 2014

Integrating multi-omics for uncovering the architecture of cross-talking pathways in breast cancer

PloS One
Li WangXia Li

Abstract

Cross-talk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. Moreover, alterations in the abnormal pathways are not limited to single molecular level. Therefore, we proposed a strategy that integrates a large number of biological sources at multiple levels for systematic identification of cross-talk among risk pathways in cancer by random walk on protein interaction network. We applied the method to multi-Omics breast cancer data from The Cancer Genome Atlas (TCGA), including somatic mutation, DNA copy number, DNA methylation and gene expression profiles. We identified close cross-talk among many known cancer-related pathways with complex change patterns. Furthermore, we identified key genes (linkers) bridging these cross-talks and showed that these genes carried out consistent biological functions with the linked cross-talking pathways. Through identification of leader genes in each pathway, the architecture of cross-talking pathways was built. Notably, we observed that linkers cooperated with leaders to form the fundamentation of cross-talk of pathways which play core roles in deterioration of breast cancer. As an example, we observed that KRAS showed a direct conn...Continue Reading

Mentioned in this Paper

Pathogenic Aspects
Biochemical Pathway
DNA Methylation [PE]
Tumor Suppressor Genes
PLK1 gene
Pathogenesis
Cross-talk
Cancer Pathway
Protein Methylation
Genome

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