RefG annotation priorities

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Rationale

Co-curation of gene families by the groups participating in the reference genome project makes several aspect of the GOC work more efficient, thus providing several advantages:

Annotation consistency, guidelines, and quality control

As the selected genes in a project will have a common theme, all curators from the different groups should generate an extended understanding of the biology in a particular area; this should help improve the consistency of annotations available for a particular system, and ontology development discussions.

Directing Ontology development

Focused co-curation will be coupled directly to ontology development work. For instance where an ontology development effort has recently generated new terms to describe a particular process, these could be provided to the group to be 'road tested' (with the understanding that terms need to be publicly available and that ontology developers are confident that a reasonable number of terms already exist in a usable state).

Where a recent ontology content meeting has generated a specific set of terms for an area of biology; co-ordinated curation work will help to rapidly generate annotations that apply the newly created terms and ensure the new terms are appropriate for all species. Annotation should be coordinated with ontology development so that external experts involved in the content meeting may also still be interested in helping with questions arising from annotation discussions.

Enable propagation of annotations via PAINT

Publicize the usefulness of the the Reference Genome initiative

Those small annotation projects will help demonstrate to external users the usefulness of the the Reference Genome initiative. Projects should aim to eventually generate targeted publications on usefulness of the GO resource with respect to a particular area of biology. For instance, a publication could compare the annotations generated for the same system across diverse species, exploring interesting differences/similarities in the data, perhaps linking up with external investigators in the chosen domain.



Defining the Reference genome biocuration projects

  • The curation priorities of the reference genome group will be based on 'biological processes', that is, either a signaling pathway, the role of a molecular complex, etc.
  • Each of those 'biocuration projects' will be lead by a 'reference genome biocuration project leader'. The project leader is a curator from a participating group that will be responsible for selecting the gene products and families involved in the selected process, provide some biological background to participating annotators, and ensure that ontology development is complete enough to undertake the project.

Requirements for these co-curation annotation projects

  1. Project proposals should be designed to create annotations to targets that are of interest to human biomedical research
  2. Proposals should include the time required for the completion of the project, aiming for a period of approximately 3-4 months. The project can be split into several subprojects if that time frame is not sufficient.
  3. At the end of this annotation period, the project should aim to generate a publication that demonstrates the usefulness of GO annotation resource and the value of the co-curation effort. The curators leading the co-curation exercise will be primary authors of such a publication as well as the Reference Genome group.
  4. The annotation effort should, if possible encourage external collaborations to use and expand the information resource provided by the co-curation effort.




Procedure for reference genome biocuration projects

  1. Once a project is agreed upon, the Projects Leader identify experts in the field.
  2. Project Leader prepares a summary of the area both to allow the selection of appropriate curation targets and to provide annotators with some basic background in the field.
  3. Project Leader identify biologically coherent targets.
  4. Project Leader must ensure that the ontology is correctly developed and work with experts to develop the ontology.
  5. MODs Curators annotate gene products targets.
  6. Tree Curators annotate families to the best of their understanding.
  7. Project leader, Tree Curators and Biological Experts meet (in person or through web-conferencing) to finalize annotations and make sure the biology is well represented.
  8. Ensure that the web presentation of the project is satisfactory
  9. Ideally, project can be published.

Projects underway

Wnt signaling Pathway

  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
  4. Project leader: Varsha Khodiyar, Suzi Lewis
  5. Possible experts: Nobue Itasaki (agreed) make sure to represent mammals, but also : fly, zebra fish, other models??
  6. Ontology status

Lung branching morphogenesis

Project leader: Li Ni, MGI (Dec 2009-Feb 2010)


Possible future Projects

Please write the name of the person(s) that would be responsible for the project. Include estimated number of genes to annotate in the species of interest, and in what time frame the annotation might be done. Add any justification (medical interest, external groups interested in collaborating, coupling with ontology development, etc).

Factors to consider in prioritization of projects

  1. How old is the family, because we can say more about ancient processes and we can cover basic biology
  2. Impact and significance of the pathway:
    1. Has implications in vertebrate biology (e.g. olfactory receptors) which can be tied to particular diseases (and include experts in these diseases as advisors). In other words, the implications and potential impact.
    2. Things that happen within a single cell (molecular)
  3. Practical aspects that will help the success of the project:
    1. Need a 'project leader' that devote the time to drive it forward
    2. There are external experts available and willing to provide feedback (i.e. outside GO, doing non-high-throughput lab work)
    3. The experimental results are easy to interpret at a molecular level: for example, the existence of a downstream reporter to measure whether the signal is coming through (the specific example here was the detection of a reporter gene that is the target of a signaling pathway, to make sure the signaling pathway was actually happening)


Signaling

When the GO editors are satisfied that the terms in this area satisfactory - curation groups could be asked to take a selection of different signaling pathways to test the structure of the ontology.



Retinoic Acid Pathway

  • Need to fix transcription factors in the ontology

Cellular processes

Autophagy

Suggested by Tanya Berardini

  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
  4. Project leader:
  5. Possible experts:
  6. Ontology status

DNA repair

Suggested by Rachael Huntley

  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
  4. Project leader:
  5. Possible experts:
  6. Ontology status

Mismatch repair pathway

Suggested by Paul Thomas

  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
    1. Pathway well conserved with homologs from E. coli to humans
    2. Well characterized biochemically and genetically
    3. Implicated in cancer
  4. Project leader:
  5. Possible experts:
    1. Samir Acharya, Ohio State U, Columbus, OH [1]
  6. Ontology status
  7. Members:
    • MutS homologs (7 total in euks, 1 family)
    • MutL homolgs (3 euks, 1 family)
    • MutH (only present in proks)
    • PCNA



P-type ATPases / copper metabolism

Suggested by Pascale Gaudet and Mike Livstone

  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
    1. Well conserved with homologs from bacteria to human
    2. The gene ATP7B is responsible for Wilson's disease.
    3. Pathway is relatively simple (?)
  4. Project leader:
  5. Possible experts:
    1. Georgina MacIntyre, University of Edmonton, Canada
  6. Ontology status

Cell polarity (and gastrulation? - cell polarity is probably enough)

Suggested by Kimberly Van Auken

  1. Justification (Impact and significance)
    1. "Polarity is an essential attribute of most eukaryotic cells." Omori and Malicki, Curr Biol, 2006.
    2. 'Furthermore, most malignant tumor cells have lost their polarity, and this is likely to play a role in both their escape from normal proliferation control and metastasis." St. Johnston and Ahringer, Cell, 2010
  2. Range of species in which the pathway is found; vertebrates, invertebrates
    1. Epithelial polarity (apical vs basolateral) - human, mouse, rat, chick, zebrafish, Drosophila, C. elegans
      1. Regulatory molecules: Crumbs, Bazooka and other PARs, aPKC
      2. Protein sorting, targeting: Cdc42, Rab GTPases
    2. Neuronal polarity (dendrite vs axon) - human, mouse, rat, Drosophila, C. elegans
      1. Regulatory molecules: LKB1 and additional PARs, SAD, STRAD
    3. Egg/oocyte polarity
  3. Species experimentally studied: human, mouse, rat, chick, zebrafish, Drosophila, C. elegans
  4. Project leader: Kimberly Van Auken
  5. Possible experts:
  6. Ontology status

Cell motility

Suggested by Pascale Gaudet

  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
  4. Project leader: x
  5. Possible experts:
  6. Ontology status

Ribosome

Suggested by Pascale Gaudet and Serenella Ferro-Rojas

  1. Justification
    1. Well conserved
    2. Rather poorly annotated (issues with : RNA being the catalyst, annotation to a complex, etc)
    3. Basic, central biological process
    4. Drug target
  2. Project leader:
  3. Possible experts:
  4. Ontology status

Protein amino acid N-linked glycosylation

Suggested by Val Wood ; see [2]

  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
  4. Project leader:
  5. Possible experts: (suggestions from Pascale; did not yet contact)
    1. Chris West, Oklahoma, USA [3]
    2. Bernard Henrissat, Marseille, France [4]
  6. Ontology status

Transcription

  • ontology needs a major fix
  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
  4. Project leader: Karen Christie
  5. Possible experts:
  6. Ontology status: Karen and David will do a major reorganization of the transcription terms in the summer 2010. We expect to be able to annotate transcription factors Aug 1, 2010.

Cell cycle

  • ontology needs a major fix
  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
  4. Project leader:
  5. Possible experts:
  6. Ontology status: needs a major fix

tRNA modification

Suggested by Pascale

  • ontology needs a major fix
  1. Justification (Impact and significance)
  2. Range of species in which the pathway if found;
  3. Species experimentally studied:
  4. Project leader:
  5. Possible experts: Valerie de Crecy-Lagard, U. of Florida [5] (suggested by Pascale; has agreed to help)
  6. Ontology status: needs a major fix; many aspects are not represented; Valerie has agreed to help on this as well.

Organ/Organismal level

Those are more difficult - we'll try the smaller projects first.

Hearing

Susan Tweedie, Doug Howe, MGI

  • A group has support for annotation/analysis of genes implicated in hearing. A suggestion would be to annotate those genes only for hearing? or we can see how many genes there are and edit all.


RefG Heart Development co-curation

  1. Project leader: Varsha Khodiar BHF-UCL
  2. Possible experts:
  3. Ontology status: Cardiovascular process GO ontology development workshop was held [dates]

Loop of Henle

  1. Project leader:
  2. Possible experts:
  3. Ontology status

The current Co-curation project for the Loop of Henle (this has been initiated by Yasmin for the Renal GO Initiative, and involves 4 curators annotating ~200 conserved orthologs found to be involved in the development of a kidney structure which differs greatly been species, see: http://wiki.geneontology.org/index.php/Loop_of_Henle_Cocuration): GOA-UniProtKB

Ageing

  1. Project leader:
  2. Possible experts:
  3. Ontology status

Transcription factors

  1. Contact: Fiona, Lakshmi
  2. Transcription factors: RUNX2, RELB, RELA, ARNTL2, AHR, JDP2, FOS, IRF3, NFKB2, E2F1, E2F4, ARNT and HMGA1


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