Network Analysis of Cancer-focused Association Network Reveals Distinct Network Association Patterns.

Cancer is a complex and heterogeneous disease. Genetic methods have uncovered thousands of complex tissue-specific mutation-induced effects and identified multiple disease gene targets. Important associations between cancer and other biological entities (eg, genes and drugs) in cancer network, however, are usually scattered in biomedical publications. Systematic analyses of these cancer-specific associations can help highlight the hidden associations between different cancer types and related genes/drugs. In this paper, we proposed a novel network-based computational framework to identify statistically over-expressed subnetwork patterns called network motifs (NMs) in an integrated cancer-specific drug-disease-gene network extracted from Semantic MEDLINE, a database containing extracted associations from MEDLINE abstracts. Eight significant NMs were identified and considered as the backbone of the cancer association network. Each NM corresponds to specific biological meanings. We demonstrated that such approaches will facilitate the formulization of novel cancer research hypotheses, which is critical for translational medicine research and personalized medicine in cancer.