Reference Genome Project

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Reference Genome Project
ZFIN
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Purpose

• - Provide comprehensive annotation for 12
  genomes
• Arabidopsis thaliana
• Caenorhabditis elegans
• Danio rerio
• Dictyostelium discoideum
• Drosophila melanogaster
• Escherichia coli
• Gallus gallus
• Homo sapiens
• Mus musculus
• Rattus norvegicus
• Saccharomyces cerevisiae
• Schizosaccharomyces pombe

• Those organisms were selected because they are
• established model organisms with published
  experimental data
• have a genome database
• have experienced GO curators

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Questions for Advisors

• What criteria should we use to collect and
  prioritize genes for the reference genomes?
• What measures would be effective for assessing
  progress on the reference genome projects?
• What level of accuracy and level of detail for
  individual genes, and coverage of all functional
  elements across the genome?

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Complete genome annotation

• Breadth every gene in the 12 genomes be
  annotated
• Depth every gene be annotated to the highest
  level of experimental knowledge in that organism

• The group has agreed that depth of annotation
  is best assessed by the curator annotating the
  gene. - If a gene has less than 5-10 papers, it
  makes sense to read and annotate all papers
• - If a gene has a lot of literature, the
  preferred strategy is to look at a recent review
  to make sure all important primary literature is
  captured more recent papers be read

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Metrics assessing breadth and depth of
annotations

• Breadth
• Number of genes (protein coding and functional
  RNAs based on SO)
• Number of genes with some functional annotation
• Number of genes with functional annotation based
  on experiments using that organism
• Number of genes with function inferred by
  sequence similarity
• Number of genes with function inferred by
  electronic annotations
• Number of genes for which there is no available
  information (root/ND annotations)
• Depth
• Number of papers linked to a gene
• Number of papers used to produce functional
  annotation
• Number of papers read but for which no new
  annotations were produced.
• Ratio of deepest annotation to leaf node to
  measure granularity and use of the ontology (Suzi)

http//gocwiki.geneontology.org/index.php/Metrics
_breath_and_depth_of_annotations
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Figures for Reference Genome genes, completely
fictitious data
Figures for Whole Genome genes, completely
fictitious data
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Mike Cherry
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(No Transcript)
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Measuring Information Content
Chris Mungall
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Information Content from an Ontology Perspective
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Priorities Selection of curation targets

• Genes that, when mutated, cause a disease
• Not included upregulated in cancer x,
  interacts with tumor suppressor y, and other
  weak evidence
• Disease gene lists - OMIM- RGD disease portal
  first group neurological diseases
• Other lists - list of common genes between
  human, fly and zebrafish that were being used as
  a test case for PATO annotations many were not
  in OMIM revisit??
• Current status trying to focus on genes with
  the broadest interest, however these often lack
  orthologs in yeast, E. coli, etc, so need to
  balance these factors.
• ADVICE HOW TO BALANCE?

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Orthologs

• Curators for each database are responsible for
  identifying orthologs of the selected gene
  (currently prioritized by OMIM disease set)
• Available tools - YOGY- InParanoid-
  OrthoMCL- TreeFam- Homologene
• Sequence analysis by curators
• REFERENCE GENOME MEETING WED THURSmajor
  discussion topic

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Software

• Google spreadsheet - shared by all curators-
  each database keeps track of putative orthologs-
  each database records the curation status for
  each gene
• Software requirements - Ensures consistent use
  of identifiers- Allow loading of MOD reports-
  Track that no ortholog was found- Provide
  reports to focus curation effort- Record that
  curation is 'comprehensive' as of a certain
  date- Allow a 1many relation between Human gene
  and MOD ortholog- Record orthology determination
  method
• Software Group currently developing

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http//rails-dev.bioinformatics.northwestern.edu2
4000/index.html
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Annotation Progress

• Curation software will be able to generate that
  information
• We would like to display the list of selected
  genes, the list of identified orthologs, the
  curation status and a way to access annotations
  (graphs)

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Annotation Consistency Comparing annotations
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(No Transcript)
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Ontology development
Number of Source Forge requests in the "Reference
Genome" group
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Outreach publicizing the reference genome effort

• Several suggestions
• GO newsletter (already have the gene of the
  quarter) could add diseases
• NCBI/OMIM could display/advertise genes with
  annotations
• Take advantage of user requests that fit nicely
  in the initiative
• Set up a reference genome wiki page showing which
  genes are coming up for annotation, which could
  also be used by researchers to suggest target
  genes
• Make a page on the GO website that would include
  diseases genes we are curating and the gene of
  the quarter articles
• Special display in AmiGO
• Provide annotations in a separate file
• Mark disease genes specifically in MODs

http//gocwiki.geneontology.org/index.php/Outreach
_publicizing_the_project_and_developing_a_web_pre
sence
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Goals for Upcoming Year

• Continued curation
• at least 250 additional genes
• Review priorities for target selection
• Software and database implemented
• Increased visibility
• Web presence
• Paper
• Integration with GO database
• Meetings
• Metrics established and tracked

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Questions for Advisors

• What criteria should we use to collect and
  prioritize genes for the reference genomes?
• What measures would be effective for assessing
  progress on the reference genome projects?
• What level of accuracy and level of detail for
  individual genes, and coverage of all functional
  elements across the genome?