Fast Bayesian Integrative Learning of Multiple Gene Regulatory Networks for Type 1 Diabetes

TL;DR

This paper introduces a fast Bayesian method for jointly estimating multiple gene regulatory networks across different conditions, specifically applied to Type 1 Diabetes, improving accuracy and efficiency over existing approaches.

Contribution

The proposed method integrates information across conditions via meta-analysis, operates on edge-wise scores for speed, and provides uncertainty measures for network edges.

Findings

Outperforms existing methods in accuracy and speed

Provides uncertainty quantification for network edges

Successfully applied to real T1D gene expression data

Abstract

Motivated by the need to study the molecular mechanism underlying Type 1 Diabetes (T1D) with the gene expression data collected from both the patients and healthy controls at multiple time points, we propose an innovative method for jointly estimating multiple dependent Gaussian graphical models. Compared to the existing methods, the proposed method has a few significant advantages. First, it includes a meta-analysis procedure to explicitly integrate information across distinct conditions. In contrast, the existing methods often integrate information through prior distributions or penalty function, which is usually less efficient. Second, instead of working on original data, the Bayesian step of the proposed method works on edge-wise scores, through which the proposed method avoids to invert high-dimensional covariance matrices and thus can perform very fast. The edge-wise score forms an equivalent measure of the partial correlation coefficient and thus provides a good summary for the graph structure information contained in the data under each condition. Third, the proposed method can provide an overall uncertainty measure for the edges detected in multiple graphical models, while the existing methods only produce a point estimate or are feasible for very small size problems. We prove consistency of the proposed method under mild conditions and illustrate its performance using simulated and real data examples. The numerical results indicate the superiority of the proposed method over the existing ones in both estimation accuracy and computational efficiency. Extension of the proposed method to joint estimation of multiple mixed graphical models is straightforward.