Efficient proximal gradient algorithm for inference of differential gene networks.

Background: Gene networks in living cells can change depending on various conditions such as caused by different environments, tissue types, disease states, and development stages. Identifying the differential changes in gene networks is very important to understand molecular basis of various biological process. While existing algorithms can be used to infer two gene networks separately from gene expression data under two different conditions, and then to identify network changes, such an approach does not exploit the similarity between two gene networks, and it is thus suboptimal. A desirable approach would be clearly to infer two gene networks jointly, which can yield improved estimates of network changes.

Results: In this paper, we developed a proximal gradient algorithm for differential network (ProGAdNet) inference, that jointly infers two gene networks under different conditions and then identifies changes in the network structure. Computer simulations demonstrated that our ProGAdNet outperformed existing algorithms in terms of inference accuracy, and was much faster than a similar approach for joint inference of gene networks. Gene expression data of breast tumors and normal tissues in the TCGA database were analyzed with our ProGAdNet, and revealed that 268 genes were involved in the changed network edges. Gene set enrichment analysis identified a significant number of gene sets related to breast cancer or other types of cancer that are enriched in this set of 268 genes. Network analysis of the kidney cancer data in the TCGA database with ProGAdNet also identified a set of genes involved in network changes, and the majority of the top genes identified have been reported in the literature to be implicated in kidney cancer. These results corroborated that the gene sets identified by ProGAdNet were very informative about the cancer disease status. A software package implementing the ProGAdNet, computer simulations, and real data analysis is available as Additional file 1.

Conclusion: With its superior performance over existing algorithms, ProGAdNet provides a valuable tool for finding changes in gene networks, which may aid the discovery of gene-gene interactions changed under different conditions.