OICR - MaRS Centre, West Tower 661 University Avenue, Suite 465 Toronto, Ontario, Canada http://oicr.on.ca/ EMBL-EBI Wellcome Trust Genome Campus Hinxton, Cambridgeshire, CB10 1SD, UK http://www.ebi.ac.uk NYU Langone Medical Center 550 1st Ave, New York, NY 10016, United States http://www.med.nyu.edu/ http://www.reactome.org Iden%ﬁers submission interface Pathway Analysis Tool Suite Fabregat A1, Weiser J2, Jupe S1, Garapati P1, Forner O1, Porras P1, Haw P2, D'Eustachio P3, Stein L2, Hermjakob H1 (1) European Bioinformatics Institute, Hinxton (UK) (2) Ontario Institute for Cancer Research, Toronto (Canada) What is Reactome? Reactome is a free, open-source, curated and peer-reviewed knowledgebase of biomolecular pathways. One of its goals is to provide intuitive bioinformatics tools for the visualization, interpretation and analysis of pathway knowledge to support basic research, genome analysis, modeling, systems biology and education. (3) NYU Langone Medical Center, New York (US) New Pathway Analysis The performance has been boosted by creating a data structure to model Reactome objects and relationships which is directly placed in memory. The data structure is composed of a radix tree (1) for the identifiers used as cross-references to the target entities, a graph (2) to model these entities and the relationships between them (like the species orthology) and double-linked trees (3) to model the hierarchy. What does the Tool Suite provide? The analysis tool suite contains an enrichment analysis, an expression data analysis and a species comparison tool. Results are presented in the Pathway Browser in tabular form within the details panel, as an overlay on pathway diagrams and hierarchy. Besides improving stability, performance, reliability and scalability to cope with future demands, we have also extended functionality. Reactome currently annotates 7,460 human proteins and 1,462 chemical compounds. The analysis tool provides an enrichment analysis for a dataset of 1,215 protein identifiers in ca. 2 seconds. The tool suite is available via a RESTFul service (http://www.reactome.org/AnalysisService/) so the different analysis can be easily integrated in third party software. 1 7 1 9 0 1 2 6 3 8 7 2 P 0 2 6 9 2 5 P10620 P10635 P10636 P11086 P60468 P60484 P05480 P10639 2 9 3 8 9 1 0 5 4 8 0 P05386 P12931 0 3 8 6 6 N E T 4 0 8 6 4 8 6 7 P12938 P12939 P11087 P10622 P29172 P60467 Mus Musculus RaDus Norvegicus Saccharomyces Cerevisae Bos Taurus Homo Sapiens Canis Familiaris Homo Sapiens Mus Musculus RaDus Norvegicus Saccharomyces Cerevisae Bos Taurus Canis Familiaris 1 2 3 1. RADIX TREE Space-optimized data structure to rapid lookup whether the target identifier is present in the Reactome data. When a identifier is found the result is a pointer(s) to the related graph node(s). 3. DOUBLE-LINKED TREE Represents the pathways and their parent-child relationships for each species in Reactome. Once the tree leaf is reached, the entity is flagged as found in each node from it to the root (unless it was flagged before). 2. ENTITIES GRAPH Represents orthology relationships between proteins of different species. Used for the projection option in order to speed up the analysis (no queries to the database are needed). ANALYSIS EXAMPLE Green arrows show use cases where the identifier is analysed in its own species. Red arrows show a use case where the identifier is projected to human during the analysis. Enrichment analysis results Expression data analysis results Contact Reactome Acknowledgements This work was supported by the US National Institutes of Health (P41 HG003751), Ontario Research Fund, the European Molecular Biology Laboratory Core Funding and the Centre for Therapeutic Target Validation (CTTV). Help Desk: help@reactome.org URL: http://www.reactome.org