title: Charting the molecular links between driver and susceptibility genes in colorectal cancer.
abstract: Despite significant advances in the identification of specific genes and pathways important in the onset and progression of colorectal cancer (CRC), mechanistic insight into the relationship between driver and susceptibility genes is needed. In this paper, we systematically explore physical interactions between causative and putative CRC susceptibility genes to reveal the molecular mechanisms involved in tumor biology. In total, we identify 622 high-confidence protein-protein interactions between 42 CRC causative and 65 candidate susceptibility genes. Among the latter, 28 are located in the CRCS9 loci, related to the etiology of CRC, and 17 are co-expressed with well-established CRC drivers, which makes them excellent candidates for further functional studies. Moreover, we find a high degree of functional coherence between connected driver and susceptibility genes, which indicates that our network-based strategy is useful to gain insight into the underlying mechanisms of those proteins with unknown roles in CRC.
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/Baldiri Reixac 10-12, Barcelona 08028, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Arroyo
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/Baldiri Reixac 10-12, Barcelona 08028, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Duran-Frigola
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/Baldiri Reixac 10-12, Barcelona 08028, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Berenguer
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/Baldiri Reixac 10-12, Barcelona 08028, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Soler-López
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/Baldiri Reixac 10-12, Barcelona 08028, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, Barcelona 08010, Spain. Electronic address: patrick.aloy@irbbarcelona.org.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aloy
mesh_terms: D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D006801:Humans; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012007:Rectum / Q000378:metabolism
chemical_list: D011506:Proteins
keywords: Colorectal cancer; Network biology; Protein interaction networks