Determining causal miRNAs and their signaling cascade in diseases using an influence diffusion model.

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Determining causal miRNAs and their signaling cascade in diseases using an influence diffusion model.

Sci Rep. 2017 08 15;7(1):8133

Authors: Nalluri JJ, Rana P, Barh D, Azevedo V, Dinh TN, Vladimirov V, Ghosh P

Abstract
In recent studies, miRNAs have been found to be extremely influential in many of the essential biological processes. They exhibit a self-regulatory mechanism through which they act as positive/negative regulators of expression of genes and other miRNAs. This has direct implications in the regulation of various pathophysiological conditions, signaling pathways and different types of cancers. Studying miRNA-disease associations has been an extensive area of research; however deciphering miRNA-miRNA network regulatory patterns in several diseases remains a challenge. In this study, we use information diffusion theory to quantify the influence diffusion in a miRNA-miRNA regulation network across multiple disease categories. Our proposed methodology determines the critical disease specific miRNAs which play a causal role in their signaling cascade and hence may regulate disease progression. We extensively validate our framework using existing computational tools from the literature. Furthermore, we implement our framework on a comprehensive miRNA expression data set for alcohol dependence and identify the causal miRNAs for alcohol-dependency in patients which were validated by the phase-shift in their expression scores towards the early stages of the disease. Finally, our computational framework for identifying causal miRNAs implicated in diseases is available as a free online tool for the greater scientific community.

PMID: 28811509 [PubMed – indexed for MEDLINE]