title: Integrating multi-omics for uncovering the architecture of cross-talking pathways in breast cancer.
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 connection to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting that it may be a central communication hub. In summary, we offer an effective way to characterize complex cross-talk among disease pathways, which can be applied to other diseases and provide useful information for the treatment of cancer.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ping
authors.affiliation: Department of Ultrasonic medicine, The 1st Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Zhao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Ultrasonic medicine, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Tian
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D001271:Atlases as Topic; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins