Fixing molecular complexes in BioPAX standards to enrich interactions and detect redundancies using semantic web technologies

Abstract

Motivation Molecular complexes play a major role in the regulation of biological pathways. The Biological Pathway Exchange format (BioPAX) facilitates the integration of data sources describing interactions some of which involving complexes. The BioPAX specification explicitly prevents complexes to have any component that is another complex (unless this component is a black-box complex whose composition is unknown). However, we observed that the well-curated Reactome pathway database contains such recursive complexes of complexes. We propose reproductible and semantically-rich SPARQL queries for identifying and fixing invalid complexes in BioPAX databases, and evaluate the consequences of fixing these non-conformities in the Reactome database. Results For the Homo sapiens version of Reactome, we identify 5,833 recursively defined complexes out of the 14,987 complexes (39%). This situation is not specific to the human dataset, as all tested species of Reactome exhibit between 30% (Plasmodium falciparum) and 40% (Sus scrofa, Bos taurus, Canis familiaris, Gallus gallus) of recursive complexes. As an additional consequence, the procedure also allows the detection of complex redundancies. Overall, this method improves the conformity and the automated analysis of the graph by repairing the topology of the complexes in the graph. This will allow to apply further reasoning methods on better consistent data. Availability We provide a jupyter notebook detailing the analysis https://github.com/cjuigne/non_conformities_detection_biopax. Supplementary information Supplementary data are available at Bioinformatics online.