LEGO June 6, 2016

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This week we will focus on the discussion of models.

Annotations/Model Discussion

Software Updates

Discussion of the Wnt signaling model

  1. Explanation of the models and the relations
  2. How will the individuals in the model chain?
  3. What annotations do we expect to get from a model like this?
  4. Is there a mechanism for limiting the annotations that are generated?
  5. How would the model differ if we had the term 'cell-cell signaling by wnt'. Draft term:

cell-cell signaling by wnt: "Any process that mediates the transfer of information from one cell to another, mediated by a wnt-family protein ligand. This process includes wnt signal transduction in the receiving cell, release of wnt ligand from a secreting cell as well as any processes that actively facilitate wnt transport and presentation to receptor on the receiving cell."

 <-- part_of wnt signaling
 <-- part_of wnt protein secretion

Question: should cell-cell signaling terms be extended to include ligand processing steps (e.g. the palmitoylation step in the above model)?

Protein Binding Annotations in Noctua

  • Use has input relation for annoton? has direct input?
    • In GAF/GPAD output, this will result in nothing in the With/From column
  • Use With/From column only?
  • Use both?

Expanding ECO use to Model Pathways More Clearly

  • For constructing pathways in LEGO, it could be useful to have more granular IGI evidence codes to support the assertion that gene products act in the same or different pathways
  • Work from the BioGrid, Princeton, and WB groups on a genetic interaction ontology might help inform this


  • On call: Chris, Dan, David H., David OS, Giulia, Heiko, Helen, Kimberly, Melanie, Midori, Sabrina, Seth

LEGO/Noctua Training

  • Next week (6/15 and 6/16) David H. and Kimberly will be conducting a LEGO training session for MGI GO curators
    • Will be both a hands-on session as well as a review of the LEGO curation manual
    • Feedback from MGI curators will hopefully guide further development of training material

Models Discussion - Causally Upstream Chains - Wnt Trafficking, Secretion, Signaling

  • We discussed the Wnt secretion model as an example of a causal network and how we want to capture annotations that may be biologically correct and relevant but several processes upstream
  • In the case of the Wnt signaling pathway, gene products involved in Wnt lipidation and transport through the endomembrane system have been annotated, by conventional GO annotation, to 'Wnt signaling pathway' but, by definition, these annotations are incorrect
  • However, there is clearly an association here that curators would like to capture, the question is, how best to do it?
  • For signaling pathways, one approach is to create new terms, for example, Wnt cell-cell signaling, that encompass the trafficking and secretion of Wnt as well as the signal transduction pathway initiated by its binding to a receptor
  • However, not every upstream process may be amenable to creation of, and inclusion within, a more encompassing parent term. In those cases, what are our options?
  • The desired extent of the causal chain for annotations may depend on the user and their perspective as a biologist, e.g. some users may want to include gene expression upstream of a given process, others may not.
  • One idea is to incorporate more causal relations in the GAF/GPAD outputs and somehow flag annotations for causally upstream processes like gene expression so that users can filter on those if they want.
  • We will continue to work on examples and discuss options.

Models Discussion - Regulates Relations - FGF Signaling Pathway and Cell Proliferation

  • We also discussed a model of fibroblast growth factor receptor signaling and its relation to cell proliferation.
  • FGFR activity is part of fibroblast growth factor receptor signaling pathway and that signaling pathway positively regulates cell proliferation
  • Curators would make an annotation for FGFR to positive regulation of cell proliferation, but the current GAF/GPAD output of this LEGO model only has the positive regulation of cell proliferation as an annotation extension in the P annotation for FGFR signaling pathway
  • The direct annotation to positive regulation of cell proliferation should be made, and can be made using the reasoner, but these annotations need to be incorporated into the GAF/GPAD files that annotation groups consume

Direct Regulation Relations

  • Now being incorporated into the ontology
  • Will need to provide curators with guidance on how these are to be used
  • Some examples:
    • provides direct input
    • directly activates
    • directly inhibits
  • Discussion of RO, go_rel - David OS, can you fill in here?