title: Protein-Protein Interactions: Gene Acronym Redundancies and Current Limitations Precluding Automated Data Integration.
abstract: Understanding protein interaction networks and their dynamic changes is a major challenge in modern biology. Currently, several experimental andin silicoapproaches allow the screening of protein interactors in a large-scale manner. Therefore, the bulk of information on protein interactions deposited in databases and peer-reviewed published literature is constantly growing. Multiple databases interfaced from user-friendly web tools recently emerged to facilitate the task of protein interaction data retrieval and data integration. Nevertheless, as we evidence in this report, despite the current efforts towards data integration, the quality of the information on protein interactions retrieved byin silicoapproaches is frequently incomplete and may even list false interactions. Here we point to some obstacles precluding confident data integration, with special emphasis on protein interactions, which include gene acronym redundancies and protein synonyms. Three human proteins (choline kinase, PPIase and uromodulin) and three different web-based data search engines focused on protein interaction data retrieval (PSICQUIC, DASMI and BIPS) were used to explain the potential occurrence of undesired errors that should be considered by researchers in the field. We demonstrate that, despite the recent initiatives towards data standardization, manual curation of protein interaction networks based on literature searches are still required to remove potential false positives. A three-step workflow consisting of: (i) data retrieval from multiple databases, (ii) peer-reviewed literature searches, and (iii) data curation and integration, is proposed as the best strategy to gather updated information on protein interactions. Finally, this strategy was applied to compilebona fideinformation on human DREAM protein interactome, which constitutes liable training datasets that can be used to improve computational predictions.
authors.affiliation: Spanish National Research Council (CSIC) - Spanish National Biotechnology Centre (CNB), Darwin 3, Cantoblanco, 28049 Madrid, Spain. jcasado@cnb.csic.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Casado-Vela
authors.affiliation: Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal. rmatthiesen@ipatimup.pt.
authors.forename: Rune
authors.initials: R
authors.lastname: Matthiesen
authors.affiliation: Alicante University, San Vicente del Raspeig Campus, 03690 Alicante, Spain. susana.selles@ua.es.
authors.forename: Susana
authors.initials: S
authors.lastname: Sellés
authors.affiliation: Spanish National Research Council (CSIC) - Spanish National Biotechnology Centre (CNB), Darwin 3, Cantoblanco, 28049 Madrid, Spain. naranjo@cnb.csic.es.|Centro Investigación Biomédica en Red (CIBERNED, Neurodegenerative disorders), Darwin 3, 28049 Madrid, Spain. naranjo@cnb.csic.es.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Naranjo
keywords: DREAM; HGNC; HUGO; KChIP3; bioinformatics; calsenilin; choline kinase; data integration; gene acronym; gene redundancy; human interactome; protein accession; protein interactions; protein-protein prediction; uromodulin