title: Systematic identification of molecular links between core and candidate genes in breast cancer.
abstract: Despite the remarkable progress achieved in the identification of specific genes involved in breast cancer (BC), our understanding of their complex functioning is still limited. In this manuscript, we systematically explore the existence of direct physical interactions between the products of BC core and associated genes. Our aim is to generate a protein interaction network of BC-associated gene products and suggest potential molecular mechanisms to unveil their role in the disease. In total, we report 599 novel high-confidence interactions among 44 BC core, 54 BC candidate/associated and 96 newly identified proteins. Our findings indicate that this network-based approach is indeed a robust inference tool to pinpoint new potential players and gain insight into the underlying mechanisms of those proteins with previously unknown roles in BC. To illustrate the power of our approach, we provide initial validation of two BC-associated proteins on the alteration of DNA damage response as a result of specific re-wiring interactions. Overall, our BC-related network may serve as a framework to integrate clinical and molecular data and foster novel global therapeutic strategies.
authors: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
authors: Rodrigo
authors: R
authors: Arroyo
authors: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
authors: Guillermo
authors: G
authors: Suñé
authors: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
authors: Andreas
authors: A
authors: Zanzoni
authors: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
authors: Miquel
authors: M
authors: Duran-Frigola
authors: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
authors: Víctor
authors: V
authors: Alcalde
authors: Genomic Instability and Cancer Laboratory, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
authors: Travis H
authors: TH
authors: Stracker
authors: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain.
authors: Montserrat
authors: M
authors: Soler-López
authors: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona 08028, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain. Electronic address: patrick.aloy@irbbarcelona.org.
authors: Patrick
authors: P
authors: Aloy
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods*; D004249:DNA Damage / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D047468:Immunoprecipitation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D020798:Two-Hybrid System Techniques
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: DNA damage response; breast cancer; network biology; protein interaction networks