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

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.

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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.


  1. Ashburner, M. et al. Nat. Genet. 25, 25–29 (2000).

    Article  CAS  Google Scholar 

  2. The Gene Ontology Consortium. Nucleic Acids Res. 47, D330–D338 (2019).

    Article  Google Scholar 

  3. Hill, D. P. et al. BMC Genomics 14, 513 (2013).

    Article  Google Scholar 

  4. Mungall, C. J., Dietze, H. & Osumi-Sutherland, D. Preprint at bioRxiv. (2014).

  5. Anindya, R., Aygün, O. & Svejstrup, J. Q. Mol. Cell 28, 386–397 (2007).

    Article  CAS  Google Scholar 

  6. Thomas, P. D. Methods Mol. Biol. 1446, 15–24 (2017).

    Article  CAS  Google Scholar 

  7. Smith, B. et al. Genome Biol. 6, R46 (2005).

    Article  Google Scholar 

  8. Chibucos, M. C., Siegele, D. A., Hu, J. C. & Giglio, M. Methods Mol. Biol. 1446, 245–259 (2017).

    Article  CAS  Google Scholar 

  9. OWL Working Group. Web Ontology Language (OWL) (OWL, 2012);

  10. Franz, M. et al. Bioinformatics 32, 309–311 (2016).

    CAS  PubMed  Google Scholar 

  11. Shannon, P. et al. Genome Res. 13, 2498–2504 (2003).

    Article  CAS  Google Scholar 

  12. Hu, Z. Curr. Protoc. Bioinformatics 45, 8.8.1–8.8.39 (2014).

    Article  Google Scholar 

  13. Gosline, S. J., Oh, C. & Fraenkel, E. Bioinformatics 31, 1124–1126 (2015).

    Article  CAS  Google Scholar 

  14. Cornish, A. J. & Markowetz, F. PLOS Comput. Biol. 10, e1003808 (2014).

    Article  Google Scholar 

  15. Xia, J., Benner, M. J. & Hancock, R. E. Nucleic Acids Res. 42, W167–W74 (2014).

    Article  CAS  Google Scholar 

  16. Chen, J., Bardes, E. E., Aronow, B. J. & Jegga, A. G. Nucleic Acids Res. 37, W305–W311 (2009).

    Article  CAS  Google Scholar 

  17. Cowley, M. J. et al. Nucleic Acids Res. 40, D862–D865 (2012).

    Article  CAS  Google Scholar 

  18. Büchel, F. et al. BMC Syst. Biol. 7, 116 (2013).

    Article  Google Scholar 

  19. Naldi, A. et al. Bioinformatics 31, 1154–1159 (2015).

    Article  CAS  Google Scholar 

  20. Le Novère, N. et al. Nat. Biotechnol. 27, 735–741 (2009).

    Article  Google Scholar 

  21. Diehl, A. D. et al. J. Biomed. Semantics 7, 44 (2016).

    Article  Google Scholar 

  22. Mungall, C. J., Torniai, C., Gkoutos, G. V., Lewis, S. E. & Haendel, M. A. Genome Biol. 13, R5 (2012).

    Article  Google Scholar 

  23. Lee, R. Y. & Sternberg, P. W. Comp. Funct. Genomics 4, 121–126 (2003).

    Article  Google Scholar 

  24. Hayamizu, T. F., Baldock, R. A. & Ringwald, M. Mamm. Genome 26, 422–430 (2015).

    Article  Google Scholar 

  25. Hastings, J. et al. Nucleic Acids Res. 44 D1, D1214–D1219 (2016).

    Article  Google Scholar 

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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



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).

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