Integrated analysis of concurrent microRNA and gene expression in the context of protein interactions

Igor Ulitsky, TAU

MicroRNAs (miRNAs) are believed to play a major role in gene regulatory networks, influencing diverse biological phenomena. Recent studies estimate that up to one third of all human genes are targeted by miRNAs, and that coordinated binding of miRNAs is frequently required for their repressive activity. A key step towards the challenge of understanding regulatory mechanisms of miRNAs in complex cellular systems is to identify functionally coherent modules of cooperating miRNAs and their targets. Inclusion of information on protein interactions and transcript levels may prove helpful in this context. We developed a novel computational method for integrated detection of modules of miRNAs, their mRNA targets, and genes consistently anticorrelated with the miRNA levels, forming coherent protein-interaction subnetworks. I will descibe our analysis of a dataset of genome-wide human mRNA and miRNA profiles, designed to identify regulatory pathways critical for self-renewal, pluripotency, and differentiation of human stem cells.

Joint work with Louise Laurent, Franz-Josef Mueller, Jeanne F. Loring and Ron Shamir.