Accurate determination of causalities in gene regulatory networks by dissecting downstream target genes.

Abstract

Accurate determination of causalities between genes is a challenge in the inference of gene regulatory networks (GRNs) from the gene expression profile. Although many methods have been developed for the reconstruction of GRNs, most of them are insufficient in determining causalities or regulatory directions. In this work, we present a novel method, namely, DDTG, to improve the accuracy of causality determination in GRN inference by dissecting downstream target genes. In the proposed method, the topology and hierarchy of GRNs are determined by mutual information and conditional mutual information, and the regulatory directions of GRNs are determined by Taylor formula-based regression. In addition, indirect interactions are removed with the sparseness of the network topology to improve the accuracy of network inference. The method is validated on the benchmark GRNs from DREAM3 and DREAM4 challenges. The results demonstrate the superior performance of the DDTG method on causality determination of GRNs compared to some popular GRN inference methods. This work provides a useful tool to infer the causal gene regulatory network.