Drug Repositioning through Systematic Mining of Gene Coexpression Networks in Cancer.
Gene coexpression network analysis is a powerful "data-driven" approach essential for understanding cancer biology and mechanisms of tumor development. Yet, despite the completion of thousands of studies on cancer gene expression, there have been few attempts to normalize and integrate co-expression data from scattered sources in a concise "meta-analysis" framework. We generated such a resource by exploring gene coexpression networks in 82 microarray datasets from 9 major human cancer types. The analysis was conducted using an elaborate weighted gene coexpression network (WGCNA) methodology and identified over 3,000 robust gene coexpression modules. The modules covered a range of known tumor features, such as proliferation, extracellular matrix remodeling, hypoxia, inflammation, angiogenesis, tumor differentiation programs, specific signaling pathways, genomic alterations, and biomarkers of individual tumor subtypes. To prioritize genes with respect to those tumor features, we ranked genes within each module by connectivity, leading to identification of module-specific functionally prominent hub genes. To showcase the utility of this network information, we positioned known cancer drug targets within the coexpression networks and predicted that Anakinra, an anti-rheumatoid therapeutic agent, may be promising for development in colorectal cancer. We offer a comprehensive, normalized and well documented collection of >3000 gene coexpression modules in a variety of cancers as a rich data resource to facilitate further progress in cancer research.
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.|IP & Science, Thomson Reuters, Boston, Massachusetts, United States of America.
Alexander E
AE
Ivliev
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Peter A C
PA
't Hoen
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
Dmitrii
D
Borisevich
Institute for General Genetics, Moscow, Russia.|George Mason University, Fairfax, VA, United States of America.|Prosapia Genetics, Solana Beach, California, United States of America.
Yuri
Y
Nikolsky
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
Marina G
MG
Sergeeva
D014408:Biomarkers, Tumor / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D057225:Data Mining / Q000379:methods; D058492:Drug Repositioning / Q000379:methods; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics*; D023281:Genomics / Q000379:methods; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D014408:Biomarkers, Tumor