title: Identifying core gene modules in glioblastoma based on multilayer factor-mediated dysfunctional regulatory networks through integrating multi-dimensional genomic data.
abstract: The driver genetic aberrations collectively regulate core cellular processes underlying cancer development. However, identifying the modules of driver genetic alterations and characterizing their functional mechanisms are still major challenges for cancer studies. Here, we developed an integrative multi-omics method CMDD to identify the driver modules and their affecting dysregulated genes through characterizing genetic alteration-induced dysregulated networks. Applied to glioblastoma (GBM), the CMDD identified a core gene module of 17 genes, including seven known GBM drivers, and their dysregulated genes. The module showed significant association with shorter survival of GBM. When classifying driver genes in the module into two gene sets according to their genetic alteration patterns, we found that one gene set directly participated in the glioma pathway, while the other indirectly regulated the glioma pathway, mostly, via their dysregulated genes. Both of the two gene sets were significant contributors to survival and helpful for classifying GBM subtypes, suggesting their critical roles in GBM pathogenesis. Also, by applying the CMDD to other six cancers, we identified some novel core modules associated with overall survival of patients. Together, these results demonstrate integrative multi-omics data can identify driver modules and uncover their dysregulated genes, which is useful for interpreting cancer genome.
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Yanyan
authors: Y
authors: Ping
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Yulan
authors: Y
authors: Deng
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Li
authors: L
authors: Wang
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Hongyi
authors: H
authors: Zhang
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Yong
authors: Y
authors: Zhang
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Chaohan
authors: C
authors: Xu
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Hongying
authors: H
authors: Zhao
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Huihui
authors: H
authors: Fan
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors: Fulong
authors: F
authors: Yu
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China xiaoyun@ems.hrbmu.edu.cn.
authors: Yun
authors: Y
authors: Xiao
authors: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China lixia@hrbmu.edu.cn.
authors: Xia
authors: X
authors: Li
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D052138:Genes, Neoplasm; D023281:Genomics / Q000379:methods*; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D025941:Protein Interaction Mapping; D016019:Survival Analysis
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