Investigating inter-chromosomal regulatory relationships through a comprehensive meta-analysis of matched copy number and transcriptomics data sets

Richard Newton, Lorenz Wernisch

Gene regulatory relationships can be inferred using matched array comparative genomics and transcriptomics data sets from cancer samples. The way in which copy numbers of genes in cancer samples are often greatly disrupted works like a natural gene amplification/deletion experiment. There are now a large number of such data sets publicly available making a meta-analysis of the data possible. We infer inter-chromosomal acting gene regulatory relationships from a meta-analysis of 31 publicly available matched array comparative genomics and transcriptomics data sets in humans. We obtained statistically significant predictions of target genes for 1430 potential regulatory genes. The regulatory relationships being inferred are either direct relationships, of a transcription factor on its target, or indirect ones, through pathways containing intermediate steps. We analyse the predictions in terms of cocitations, both publications which cite a regulator with any of its inferred targets and cocitations of any genes in a target list. The most striking observation from the results is the greater number of inter-chromosomal regulatory relationships involving repression compared to those involving activation. The complete results of the meta-analysis are presented in the database METAMATCHED. We anticipate that the predictions contained in the database will be useful in informing experiments and in helping to construct networks of regulatory relationships.