In many cancers, mechanisms of gene regulation can be severely altered. Identification of deregulated genes, which do not follow the regulation processes that exist between transcription factors and their target genes, is of importance to better understand the development of the disease. We propose a methodology to detect deregulation mechanisms with a particular focus on cancer subtypes. This strategy is based on the comparison between tumoral and healthy cells. First, we use gene expression data from healthy cells to infer a reference gene regulatory network. Then, we compare it with gene expression levels in tumor samples to detect deregulated target genes. We finally measure the ability of each transcription factor to explain these deregulations. We apply our method on a public bladder cancer data set derived from The Cancer Genome Atlas project and confirm that it captures hallmarks of cancer subtypes. We also show that it enables the discovery of new potential biomarkers.
Keywords: Cancer systems biology; deregulations; gene regulatory network.