Infer miRNA-mRNA interactions using paired expression data from a single sample

MicroRNAs (miRNAs) are small (∼ 22 nucleotides) RNA molecules that base-pair with mRNA primarily at the 3′ untranslated region (UTR) to cause mRNA degradation or translational repression (Bartel [2009]). The expression levels of miRNA and mRNA are usually measured by microarray or RNA-seq. Paried expression profiling of both miRNA and mRNA enables identifying miRNA-mRNA interactions within an individual and calls for a new computational method. We develop Roleswitch to infer Probabilities of MiRNA-mRNA Interaction Signature (ProMISe) using paired expression data from a single sample (paper in preparation). Roleswitch takes as inputs two expression vectors of N mRNAs and M miRNAs and a N ×M seed match matrix containing the number of target sites for each mRNA i and miRNA k. The program then outputs a probability matrix that mRNA i (row) being a target of miRNA k (column). User can provide roleswitch() with a seed-match matrix. Otherwise, getSeedMatrix will be invoked to retrieve seed-match matrix from existing (online) database. Briefly, Roleswitch operates in two phases by inferring the probabilities of mRNA (miRNA) being the targets ("targets") of miRNA (mRNA), taking into account the expression of all of the mRNAs (miRNAs) due to their potential competition for the same miRNA (mRNA). Due to mRNA transcription and miRNA repression events simutaneously happening in the cell, Roleswitch assumes that the total transcribed mRNA levels are higher than the observed (equilibrium) mRNA levels and iteratively updates the total transcription of each mRNA targets based on the above inference. Based on our extensive tests on cancer data from TCGA, Roleswitch identifies more validated targets comparing with existing methods (paper in preparation). Additionally, the inferred ProMISe rivals expression profiles in cancer diagnosis yet provides unique opportunities to explore oncogenic mRNA-miRNA interactions (paper in preparation). The algorithm is outlined as follow: