Bayesian differential analysis of gene regulatory networks exploiting genetic perturbations

Yan Li,Tengfei Li,Dayou Liu,Yungang Zhu

doi:10.1186/s12859-019-3314-3

Abstract

BackgroundGene regulatory networks (GRNs) can be inferred from both gene expression data and genetic perturbations. Under different conditions, the gene data of the same gene set may be different from each other, which results in different GRNs. Detecting structural difference between GRNs under different conditions is of great significance for understanding gene functions and biological mechanisms.ResultsIn this paper, we propose a Bayesian Fused algorithm to jointly infer differential structures of GRNs under two different conditions. The algorithm is developed for GRNs modeled with structural equation models (SEMs), which makes it possible to incorporate genetic perturbations into models to improve the inference accuracy, so we name it BFDSEM. Different from the naive approaches that separately infer pair-wise GRNs and identify the difference from the inferred GRNs, we first re-parameterize the two SEMs to form an integrated model that takes full advantage of the two groups of gene data, and then solve the re-parameterized model by developing a novel Bayesian fused prior following the criterion that separate GRNs and differential GRN are both sparse.ConclusionsComputer simulations are run on synthetic data to compare BFDSEM to two state-of-the-art joint inference algorithms: FSSEM and ReDNet. The results demonstrate that the performance of BFDSEM is comparable to FSSEM, and is generally better than ReDNet. The BFDSEM algorithm is also applied to a real data set of lung cancer and adjacent normal tissues, the yielded normal GRN and differential GRN are consistent with the reported results in previous literatures. An open-source program implementing BFDSEM is freely available in Additional file 1.

Highlights

Gene regulatory networks (GRNs) can be inferred from both gene expression data and genetic perturbations
Both fused sparse SEM (FSSEM) and ReDNet made joint differential analysis for directed GRNs modeled with Structural equation model (SEM), their simulation studies demonstrated that FSSEM and ReDNet significantly outperformed naive approaches based on SML [13] and 2SPLS [22], respectively
We propose a Bayesian Fused Differential analysis algorithm for GRNs modeled with SEMs (BFDSEM) to jointly infer pair-wise GRNs under different conditions

Summary

Introduction

Gene regulatory networks (GRNs) can be inferred from both gene expression data and genetic perturbations. Mohan et al [17] and Danaher et al [18] proposed penalized algorithms based on multiple Gaussian graphical models to jointly infer GRNs under different conditions exploiting the similarities and differences between them. Ren and Zhang [21] proposed a re-parametrization based differential analysis algorithm for SEMs (ReDNet), they re-parameterized the pair-wise SEMs as one integrated SEM incorporating the averaged GRN and differential GRN, and identified the difference GRN directly from the integrated model Both FSSEM and ReDNet made joint differential analysis for directed GRNs modeled with SEMs, their simulation studies demonstrated that FSSEM and ReDNet significantly outperformed naive approaches based on SML [13] and 2SPLS [22], respectively

Methods

Results

Discussion

Conclusion