The Apoptosis Gene Ontology project and the IntAct-Apoptosis dataset: updating the conceptual representation of apoptosis.

The comprehensive and detailed analysis and depiction of biological pathways and reactions requires the use of resources and databanks in which previous knowledge is stored in an organized and standardized way and made available for the scientific community. Resources such as protein and gene databanks, molecular interactions databases or annotation ontologies used to characterize genes and gene products help to provide researchers with a reference from which they can infer current scientific knowledge, expanding and annotating their own datasets. As participants in the APO-SYS Consortium (www.apo-sys.eu/), a project funded by the European Community to focus on “Apoptosis Systems Biology Applied to Cancer and AIDS”, the molecular interactions database IntAct (www.ebi.ac.uk/intact) and the Gene Ontology (GO, www.geneontology.org) have taken a significant effort to improve annotation and representation of apoptotic cell death in their respective domains. Both resources are hosted at the European Bioinformatics Institute (EBIEMBL). IntAct is currently one of the biggest primary repositories of molecular interactions, hosting more than 300.000 binary interaction evidences represented with a high level of detail and extracted from the manual curation of over 5.700 publications. The GO project is an international effort with the aim to consistently and systematically annotate gene products by using a controlled vocabulary. Annotations performed with this ontology help representing and interpreting biological data both in detailed, small-scale setups and in the comprehensive, ‘omics’-sized studies that have revolutionized our understanding of biology in the last 10-15 years. GO term annotation and GO enrichment analysis have become fundamental tools in the study of protein-protein interaction networks. The research groups involved in the APO-SYS Consortium highlighted the need for a thorough revision of apoptosis-related terms in GO in order to properly depict current knowledge in the field. In a collaborative effort, members of the IntAct and the GO teams at the EBI have undertaken a guided curation effort of literature recommended by the consortium experts, creating more granular terms that can accurately represent the scientific consensus in apoptosis. Old, inaccurate terms have been updated or obsoleted and the relationships between both updated and newly created terms have been thoroughly revised. A major re-annotation effort with the goal to increase the granularity and extension of current annotations has already