Maximal entropy random walk on heterogenous network for MIRNA-disease Association prediction

• Published in: Mathematical biosciences 2018-12, Vol.306, p.1-9
• Main Authors: Niu, Ya-Wei, Liu, Hua, Wang, Guang-Hui, Yan, Gui-Ying
• Format: Article
• Language: English
• Subjects: Cancer; Computational Biology; Computer applications; Computer Simulation; Databases, Nucleic Acid - statistics & numerical data; Disease; Diseases; Entropy; Esophagus; Female; Gene Regulatory Networks; Genetic Predisposition to Disease; Heterogenous network; Humans; Lung cancer; Lymphoma; Male; Mathematical models; Maximal entropy random walk; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miRNA-disease association; Models, Genetic; Neoplasms - genetics; Predictive Value of Tests; Prostate cancer; Quality assessment; Random walk
• ISSN: 0025-5564; 1879-3134
• DOI: 10.1016/j.mbs.2018.10.004

•MERWMDA was an innovative and efficient research practice by introducing maximal random walk into field of disease-miRNA association prediction.•MERWMDA adopted a simple but effective way by integrating multi-resource datasets into a heterogenous network comprised of diseases and miRNA, full of information.•MERWMDA was an unsupervised method, and it could be conducted for new diseases without known miRNA associations.•A relatively high proportion of predicted disease-related miRNAs by MERWMDA were confirmed by recent experiment literature. The last few decades have verified the vital roles of microRNAs in the development of human diseases and witnessed the increasing interest in the prediction of potential disease-miRNA associations. Owning to the open access of many miRNA-related databases, up until recently, kinds of feasible in silico models have been proposed. In this work, we developed a computational model of Maximal Entropy Random Walk on heterogenous network for MiRNA-disease Association prediction (MERWMDA). MERWMDA integrated known disease-miRNA association, pair-wise functional relation of miRNAs and pair-wise semantic relation of diseases into a heterogenous network comprised of disease and miRNA nodes full of information. As a kind of widely-applied biased walk process with more randomness, MERW was then implemented on the heterogenous network to reveal potential disease-miRNA associations. Cross validation was further performed to evaluate the performance of MERWMDA. As a result, MERWMDA obtained AUCs of 0.8966 and 0.8491 respectively in the aspect of global and local leave-one-out cross validation. What’ more, three different case study strategies on four human complex diseases were conducted to comprehensively assess the quality of the model. Specifically, one kind of case study on Esophageal cancer and Prostate cancer were conducted based on HMDD v2.0 database. 94% and 88% out of the top 50 ranked miRNAs were confirmed by recent literature, respectively. To simulate new disease without known related miRNAs, Lung cancer (confirmed ratio 94%) associated miRNAs were removed for case study. Lymphoma (verified ratio 88%) was adopted to assess the prediction robustness of MERWMDA based on HMDD v1.0 database. We anticipated that MERWMDA could offer valuable candidates for in vitro biomedical experiments in future.