Reference Genome Meeting Minutes April 2008

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April 20, 2008

Annotation Progress (Mike Cherry)

  • Number of annotated genes per organism by evidence type (overall)
    • Compare graphs for Sept 2007 and Apr 2008 - overall size and size the same, but IEA decreasing

Discussion: What is effort/person? X-axis is absolute number of genes, which doesn't reflect differences in genome size.

  • Number of annotated genes per organism by evidence code for Reference Genome project
    • majority of genes have experimental evidence codes
  • Discussion:
    • Graph needs outline that indicates "no ortholog". This allows a comparison of the genes present or absent in the reference genome genomes. It will also show which organisms are lagging behind.
    • Number of annotations as a metric? would give a different view of the progress, but too variable b/c of differences in depth of knowledge in different organisms, different areas of the ontology.
    • View progress between Sept 2007 and April 2008 as a % change. Can see that everyone has doubled experimental annotations, although it doesn't show the starting number of annotations.
    • Need to discuss which metrics we want to track and why. Need consistent measures across groups.
    • How annotations change over time lets you see whether groups are still engaged in the process.
    • Would be useful to have a display that shows how much is known about these genes. Some of this information will come from Chris's reports.

Annotation Progress (Chris Mungall)

Metrics:

distance to leaf

information content

coverage

publications per gene

GO terms per gene

Review Annotation Pipeline proposal (Suzi)

Step 1: Generation of protein sets (excluding functional RNAs)

    • How to define a coherent set For experimental annotations, want to annotate to isoforms. But for tree building want longest protein produced from a gene. So for ortho sets want a unique protein/gene ID for the "canonical" gene/protein.
      • Currently there is heterogeneity in column 2 of Gene Association files (see Annotation of alternate spliceforms)
        • How does UniProt deal with alternate splice forms? Most of the time, there is a 1:1 correspondence between the canonical protein ID and the gene. Uniprot uses canonical identifier followed by -1, -2, etc to indicate isoforms. But sometimes isoforms are so different that they are given separate accessions. In that case, what connects them? have to link out to genomic database.
        • WormBase uses a mixture of gene and protein IDs in column 2. Which is used depends upon how the experiments were done. Is this a problem? Goal would be converge on one type.
        • MGI uses canonical MGI IDs in column 2.
      • Chris's Proposal: Use canonical ID in column 2. Add additional column for isoforms; put multiple isoform IDs on one line.

Column 2: Use canonical gene ID. Gene Index Column 17: ID for the thing that was annotated (protein/gene/transcript). Must match column 12 (SO type).

        • Discussion:

Add a column that is always for a gene. A gene is a "concept", it's a lumping term that reflects biological reality. It provides the link we want.

Rex's proposal:

    Column 2:  Keep as is, the ID for thing that was annotated.  (ideally would be the gene product)
    Column 12: keep is it is, because it refers to column 2
    Add Column 17: Canonical ID for the gene that codes for the product that was annotated.    


Have to look at how any change will affect our users.

    What do users expect to be in column 2?  they expect canonical ID, but it isn't always the case. 

Most groups in favor of the proposal of making column 2 the canonical ID.

        • What should column 12 refer to?

Point to 17, which means that column 17 must be filled in; it can't be left blank and inferred from column 2.)

        • Notifying users

Before change is implemented, should it be discussed with a few users?

Need a pushout list to identify users of changes/updates.


      • Still need gene to protein associations
    right now it is a free-floating column 18

gene association file should be gene association file

gp2protein file should be separate

Proposal: The header of gene association file should state this file contains annotations for x out of total number of genes estimated in this organism.

gp2protein file : For every canonical gene ID there will be an associated canonical protein ID.

What about those cases where gene has been annotated, but there is no known protein sequence associated with it. Leave blank? or explicitly state "uncloned?"

state that no protein has been identified for gene that was identified split out functional RNAs that have been identified

gp2protein: 123 AA sequence Accession (UniprotKB:xxx or NCBI:xxx) 456 RNA 789 uncloned

Don't want to overload the file (putting non ID information in an ID column). If needed, should make a separate file or find other ways of dealing with the blanks. Can generate report that gives type from column 12.

If gp2protein file has only canonical protein IDs, how do you get information about other protein IDs (column 17)?

review: GAF column 2 is canonical gene ID

   column 17 is thing you are annotating (always required)
   column 12 matches column 17 and contains SO ID's

gp2protein file: 1) includes complete gene index (except for pseudogenes and transposons)

  column 1 is canonical gene ID
  column 2 is accession for sequence of longest form of protein from UniProtKB: or NCBI: 

Action items:

1) update documentation

2) write notice of changes to users

3) individual data providers make sure that their input matches

4) software changes as necessary

5) add header to gene association file

6) syntex of file will be provided by Mike and Chris

Step 2: Experimental Annotation

Step 3: Inferential Annotation

Step 4: Quality Checks