title: The pan-cancer pathological regulatory landscape.
abstract: Dysregulation of the normal gene expression program is the cause of a broad range of diseases, including cancer. Detecting the specific perturbed regulators that have an effect on the generation and the development of the disease is crucial for understanding the disease mechanism and for taking decisions on efficient preventive and curative therapies. Moreover, detecting such perturbations at the patient level is even more important from the perspective of personalized medicine. We applied the Transcription Factor Target Enrichment Analysis, a method that detects the activity of transcription factors based on the quantification of the collective transcriptional activation of their targets, to a large collection of 5607 cancer samples covering eleven cancer types. We produced for the first time a comprehensive catalogue of altered transcription factor activities in cancer, a considerable number of them significantly associated to patient's survival. Moreover, we described several interesting TFs whose activity do not change substantially in the cancer with respect to the normal tissue but ultimately play an important role in patient prognostic determination, which suggest they might be promising therapeutic targets. An additional advantage of this method is that it allows obtaining personalized TF activity estimations for individual patients.
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain.
authors.forename: Matias M
authors.initials: MM
authors.lastname: Falco
authors.affiliation: Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, CB2 0QQ, Cambridge, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Bleda
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Carbonell-Caballero
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain.|Functional Genomics Node (INB-ELIXIR-es), C/Eduardo Primo Yufera 3, Valencia, 46012, Spain.|Bioinformatics in Rare Diseases (BiER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), C/Eduardo Primo Yufera 3, Valencia, 46012, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D014157:Transcription Factors