Improving GRN re-construction by mining hidden regulatory signals.

Inferring gene regulatory networks (GRNs) from gene expression data is an important but challenging issue in systems biology. Here, the authors propose a dictionary learning-based approach that aims to infer GRNs by globally mining regulatory signals, known or latent. Gene expression is often regulated by various regulatory factors, some of which are observed and some of which are latent. The authors assume that all regulators are unknown for a target gene and the expression of the target gene can be mapped into a regulatory space spanned by all the regulators. Specifically, the authors modify the dictionary learning model, k -SVD, according to the sparse property of GRNs for mining the regulatory signals. The recovered regulatory signals are then used as a pool of regulatory factors to calculate a confidence score for a given transcription factor regulating a target gene. The capability of recovering hidden regulatory signals was verified on simulated data. Comparative experiments for GRN inference between the proposed algorithm (OURM) and some state-of-the-art algorithms, e.g. GENIE3 and ARACNE, on real-world data sets show the superior performance of OURM in inferring GRNs: higher area under the receiver operating characteristic curves and area under the precision-recall curves.