Large-scale inference of gene function through phylogenetic annotation of Gene Ontology terms: case study of the apoptosis and autophagy cellular processes.

Journal: Database : the journal of biological databases and curation
Published Date: Dec 26, 2016

Abstract

We previously reported a paradigm for large-scale phylogenomic analysis of gene families that takes advantage of the large corpus of experimentally supported Gene Ontology (GO) annotations. This 'GO Phylogenetic Annotation' approach integrates GO annotations from evolutionarily related genes across ∼100 different organisms in the context of a gene family tree, in which curators build an explicit model of the evolution of gene functions. GO Phylogenetic Annotation models the gain and loss of functions in a gene family tree, which is used to infer the functions of uncharacterized (or incompletely characterized) gene products, even for human proteins that are relatively well studied. Here, we report our results from applying this paradigm to two well-characterized cellular processes, apoptosis and autophagy. This revealed several important observations with respect to GO annotations and how they can be used for function inference. Notably, we applied only a small fraction of the experimentally supported GO annotations to infer function in other family members. The majority of other annotations describe indirect effects, phenotypes or results from high throughput experiments. In addition, we show here how feedback from phylogenetic annotation leads to significant improvements in the PANTHER trees, the GO annotations and GO itself. Thus GO phylogenetic annotation both increases the quantity and improves the accuracy of the GO annotations provided to the research community. We expect these phylogenetically based annotations to be of broad use in gene enrichment analysis as well as other applications of GO annotations.Database URL: http://amigo.geneontology.org/amigo.

Authors

  • Marc Feuermann
    Swiss-Prot group.
  • Pascale Gaudet
    Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland, Department of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, SIB Swiss Institute of Bioinformatics, 1 Rue Michel Servet, 1211 Geneva, Switzerland, Department of Medicine and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA, School of Information, University of South Florida, Tampa, FL, 33647, USA, Genomics Division, Lawrence Berkeley National Lab, 1 Cyclotron Rd., Berkeley, 94720 CA USA, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK, Swiss-Prot Group, SIB Swiss Institute of Bioinformatics, Centre Medical Universitaire, Geneva, Switzerland, ETH Zurich, Department of Computer Science, Universitätstr. 19, 8092 Zürich, Switzerland, SIB Swiss Institute of Bioinformatics, Universitätstr. 6, 8092 Zürich, Switzerland and University College London, Gower St, London WC1E 6BT, UK.
  • Huaiyu Mi
    Division of Bioinformatics, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA and.
  • Suzanna E Lewis
    Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland, Department of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, SIB Swiss Institute of Bioinformatics, 1 Rue Michel Servet, 1211 Geneva, Switzerland, Department of Medicine and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA, School of Information, University of South Florida, Tampa, FL, 33647, USA, Genomics Division, Lawrence Berkeley National Lab, 1 Cyclotron Rd., Berkeley, 94720 CA USA, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK, Swiss-Prot Group, SIB Swiss Institute of Bioinformatics, Centre Medical Universitaire, Geneva, Switzerland, ETH Zurich, Department of Computer Science, Universitätstr. 19, 8092 Zürich, Switzerland, SIB Swiss Institute of Bioinformatics, Universitätstr. 6, 8092 Zürich, Switzerland and University College London, Gower St, London WC1E 6BT, UK.
  • Paul D Thomas
    Division of Bioinformatics, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA and.

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