Identification of self-regulatory network motifs in reverse engineering gene regulatory networks using microarray gene expression data

Abstract

Gene Regulatory Networks (GRNs) are reconstructed from the microarray gene expression data through diversified computational approaches. This process ensues in symmetric and diagonal interaction of gene pairs that cannot be modelled as direct activation, inhibition, and self-regulatory interactions. The values of gene co-expressions could help in identifying co-regulations among them. The proposed approach aims at computing the differences in variances of co-expressed genes rather than computing differences in values of mean expressions across experimental conditions. It adopts multivariate co-variances using principal component analysis (PCA) to predict an asymmetric and non-diagonal gene interaction matrix, to select only those gene pair interactions that exhibit the maximum variances in gene regulatory expressions. The asymmetric gene regulatory interactions help in identifying the controlling regulatory agents, thus lowering the false positive rate by minimizing the connections between previously unlinked network components. The experimental results on real as well as in silico datasets including time-series RTX therapy, Arabidopsis thaliana, DREAM-3, and DREAM-8 datasets, in comparison with existing state-of-the-art approaches demonstrated the enhanced performance of the proposed approach for predicting positive and negative feedback loops and self-regulatory interactions. The generated GRNs hold the potential in determining the real nature of gene pair regulatory interactions.

Keywords: asymmetric gene regulatory interactions; biology computing; co-expressed genes; controlling regulatory agents; diagonal interaction; diversified computational approaches; gene co-expressions; gene pair regulatory interactions; gene pairs; gene regulatory expressions; genetics; interacting genes; mean expressions; microarray gene expression data; molecular biophysics; principal component analysis; reverse engineering; reverse engineering gene regulatory networks; self-regulatory interactions; self-regulatory network motifs; symmetric interaction; unlinked network components.