Bayesian Analysis for miRNA and mRNA Interactions Using Expression Data

Abstract

MicroRNAs (miRNAs) are small RNA molecules composed of 19-22 nt, which play important regulatory roles in post-transcriptional gene regulation by inhibiting the translation of the mRNA into proteins or otherwise cleaving the target mRNA. Inferring miRNA targets provides useful information for understanding the roles of miRNA in biological processes that are potentially involved in complex diseases. Statistical methodologies for point estimation, such as the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm, have been proposed to identify the interactions of miRNA and mRNA based on sequence and expression data. In this paper, we propose using the Bayesian LASSO (BLASSO) and the non-negative Bayesian LASSO (nBLASSO) to analyse the interactions between miRNA and mRNA using expression data. The proposed Bayesian methods explore the posterior distributions for those parameters required to model the miRNA-mRNA interactions. These approaches can be used to observe the inferred effects of the miRNAs on the targets by plotting the posterior distributions of those parameters. For comparison purposes, the Least Squares Regression (LSR), Ridge Regression (RR), LASSO, non-negative LASSO (nLASSO), and the proposed Bayesian approaches were applied to four public datasets. We concluded that nLASSO and nBLASSO perform best in terms of sensitivity and specificity. Compared to the point estimate algorithms, which only provide single estimates for those parameters, the Bayesian methods are more meaningful and provide credible intervals, which take into account the uncertainty of the inferred interactions of the miRNA and mRNA. Furthermore, Bayesian methods naturally provide statistical significance to select convincing inferred interactions, while point estimate algorithms require a manually chosen threshold, which is less meaningful, to choose the possible interactions.