Using OWL reasoning to support the generation of novel gene sets for enrichment analysis.

Journal: Journal of biomedical semantics
Published Date: Feb 14, 2018

Abstract

BACKGROUND: The Gene Ontology (GO) consists of over 40,000 terms for biological processes, cell components and gene product activities linked into a graph structure by over 90,000 relationships. It has been used to annotate the functions and cellular locations of several million gene products. The graph structure is used by a variety of tools to group annotated genes into sets whose products share function or location. These gene sets are widely used to interpret the results of genomics experiments by assessing which sets are significantly over- or under-represented in results lists. F Hoffmann-La Roche Ltd. has developed a bespoke, manually maintained controlled vocabulary (RCV) for use in over-representation analysis. Many terms in this vocabulary group GO terms in novel ways that cannot easily be derived using the graph structure of the GO. For example, some RCV terms group GO terms by the cell, chemical or tissue type they refer to. Recent improvements in the content and formal structure of the GO make it possible to use logical queries in Web Ontology Language (OWL) to automatically map these cross-cutting classifications to sets of GO terms. We used this approach to automate mapping between RCV and GO, largely replacing the increasingly unsustainable manual mapping process. We then tested the utility of the resulting groupings for over-representation analysis.

Authors

  • David J Osumi-Sutherland
    European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, CB10 1SD, UK. davidos@ebi.ac.uk.
  • Enrico Ponta
    Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, -4070, Basel, CH, Switzerland.
  • Mélanie Courtot
    Molecular Biology and Biochemistry Department, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada, Department of Neurology, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY 14203, USA, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA, Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA, School of Dental Medicine, University at Buffalo, NY 14214-8006, USA, J. Craig Venter Institute, La Jolla, CA 92037, USA, Department of Pathology, University of California, San Diego, CA 92093, USA.
  • Helen Parkinson
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Laura Badi
    Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, -4070, Basel, CH, Switzerland.

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