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Gene Ontology Causal Activity Modeling (GO-CAM) moves beyond GO annotations to structured descriptions of biological functions and systems

Nature Genetics volume 51, pages 1429–1433 (2019)Cite this article

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To increase the utility of Gene Ontology (GO) annotations for interpretation of genome-wide experimental data, we have developed GO-CAM, a structured framework for linking multiple GO annotations into an integrated model of a biological system. We expect that GO-CAM will enable new applications in pathway and network analysis, as well as improve standard GO annotations for traditional GO-based applications.

The GO was created as a computational structure for conceptualizing and describing gene function1. The broad aims were first to create an ontology of gene function, that is, a comprehensive set of terms and relationships between them, and second to support functional annotation of genes. When the GO was first developed, the first whole genomes were being sequenced, and statements about gene function were conceived of as ‘annotations’ in the ‘book’ of the genome. The goal was to apply a consistent set of concepts describing gene function to a broad range of eukaryotic model organisms (which were later extended to prokaryotes and viruses). This application would enable the identification of evolutionarily shared genetic programs, with the ultimate goal being to shed light on the functions of human genes on the basis of knowledge about genes in model organisms.

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Fig. 1: Standard GO annotations versus the GO-CAM model.
Fig. 2: An overview of the structured representation defined by GO-CAM.
Fig. 3: GO-CAM model of initial steps in the canonical Wnt signaling pathway.

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Acknowledgements

This work was supported by NIH NHGRI grant U41 HG002273 (co-funded by NIGMS) to the Gene Ontology Consortium (principal investigators J. Blake, J. Cherry, C. Mungall, P. Sternberg and P. Thomas). The authors would like to thank P. D’Eustachio for helpful discussions, T. Mushayahama for work on the Noctua user interface, D. Ebert for work on conversion of standard annotations to GO-CAM and all the GO curators who have extensively tested the GO-CAM framework and provided valuable feedback on it and on the Noctua tool: S. Aleksander, G. Antonazzo, H. Attrill, T. Berardini, L. Breuza, A. Bridge, A. Britan, J. Cho, K. Christie, M. Courtot, I. Cusin, B. Czub, H. Dietze, P. Jaiswal, R. Dodson, H. Drabkin, S. Engel, P. Fey, M. Feuermann, M. Fisher, P. Garmiri, G. Georghiou, D. Gonzalez, C. Grove, E. Hatton-Ellis, M. Harris, M.-C. Harrison, J. Hayles, T. Hayman, V. Hinard, D. Howe, X. Huang, R. Huntley, H. Bye-A-Jee, R. Kishore, O. Lang, R. Lee, A. Lock, R. Lovering, A. MacDougall, M. Martin, P. Masson, J. Mendel, M. Munoz-Torres, R. Nash, L. Ni, A. Nikjenad, C. O’Donovan, B. Palka, C. Pich, K. Pichler, S. Poux, L. Reiser, P. Roncaglia, T. Sawford, A. Shypitsyna, D. Sitnikov, E. Speretta, N. Tyagi, S. Toro, M. Tuli, K. Warner, E. Wong, V. Wood and R. Zaru.

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Authors and Affiliations

  1. Department of Preventive Medicine, Division of Bioinformatics, University of Southern California, Los Angeles, CA, USA

    Paul D. Thomas, Huaiyu Mi & Laurent-Philippe Albou

  2. The Jackson Laboratory, Bar Harbor, ME, USA

    David P. Hill

  3. European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK

    David Osumi-Sutherland

  4. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA

    Kimberly Van Auken

  5. Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Seth Carbon, Benjamin Good, Suzanna E. Lewis & Christopher J. Mungall

  6. Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    James P. Balhoff

  7. SIB Swiss Institute of Bioinformatics, Geneva, Switzerland

    Pascale Gaudet

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  1. Paul D. Thomas
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Contributions

P.D.T. conceived the framework and supervised its development. C.J.M. developed the OWL representation, to which D.O.S. and J.P.B. contributed, and supervised software implementation. H.M. developed the framework specification and alignment with SBGN. D.O.-S., D.P.H., K.v.A. and P.G. refined the GO to ensure compatibility with the framework. D.P.H., K.v.A. and P.G. extended the framework to cover multiple types of biological systems and tested the curation software. S.C. designed the Noctua curation software, and S.C., J.P.B. and B.G. implemented the back-end software and OWL representation. L.-P.A. implemented the public-facing interface, performed quality control and developed queries for the GO-CAM repository. S.E.L. helped supervise software implementation. P.D.T. and C.J.M. wrote the paper, incorporating input from all authors.

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Correspondence to Paul D. Thomas.

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Thomas, P.D., Hill, D.P., Mi, H. et al. Gene Ontology Causal Activity Modeling (GO-CAM) moves beyond GO annotations to structured descriptions of biological functions and systems. Nat Genet 51, 1429–1433 (2019). https://doi.org/10.1038/s41588-019-0500-1

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