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 nonconformities in the Reactome database. RESULTS: For the Homo sapiens version of Reactome, we identify 5833 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, and 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 AND IMPLEMENTATION: We provide a Jupyter notebook detailing the analysis https://github.com/cjuigne/non_conformities_detection_biopax.

SUMMARY: PAX2GRAPHML is an open-source Python library that allows to easily manipulate BioPAX source files as regulated reaction graphs described in.graphml format. The concept of regulated reactions, which allows connecting regulatory, signaling and metabolic levels, has been used. Biochemical reactions and regulatory interactions are homogeneously described by regulated reactions involving substrates, products, activators and inhibitors as elements. PAX2GRAPHML is highly flexible and allows generating graphs of regulated reactions from a single BioPAX source or by combining and filtering BioPAX sources. Supported by the graph exchange format .graphml, the large-scale graphs produced from one or more data sources can be further analyzed with PAX2GRAPHML or standard Python and R graph libraries. AVAILABILITY AND IMPLEMENTATION: https://pax2graphml.genouest.org.