Meta-Analysis on Gene Regulatory Networks Discovered by Pairwise Granger Causality

Abstract—Identifying regulatory genes partaking in disease development is important to medical advances. Since gene expression data of multiple experiments exist, combining results from multiple gene regulatory network discoveries offers higher sensitivity and specificity. However, data for multiple experiments on the same problem may not possess the same set of genes, and hence many existing combining methods are not applicable. In this paper, we approach this problem using a number of meta-analysis methods and compare their performances. Simulation results show that vote counting is outperformed by methods belonging to the Fisher’s chi-square (FCS) family, of which FCS test is the best. Applying FCS test to the real human HeLa cell-cycle dataset, degree distributions of the combined network is obtained and compared with previous works. Consulting the BioGRID database reveals the biological relevance of gene regulatory networks discovered using the proposed method. Keywords—gene regulatory network; meta-analysis; multiple experiments; pairwise Granger causality; Fisher’s chi-square test I