Ref Gen pub draft (Retired)

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The Reference Genome Annotation Project

Introduction

We are experiencing an explosion of genomic information, where more and more genomes are being sequenced. However, there are limited resources to annotate these growing numbers of genomes, thus automatic annotation will be the method of choice for many. On the other side, several model organism databases have a group of trained and highly skilled GO curators. In an effort to maximize and optimize the GO annotation of a large set of key genomes (called from now on 'the reference genomes') the GO consortium has established the priority goal to completely annotate 12 reference genomes. These reference genomes are:

The Reference Genome GO Annotation Team, with representatives from each genome annotation group, coordinates annotation, facilitates implementation of GO Consortium annotation priorities, and provides quantitative measures to assess progress toward the goal of broad and deep annotation of the reference genomes. This group represents the annotation expertise within the GO consortium and provides key liaisons to the model organism databases that have primary responsibilities for the annotation of the reference genomes.

Priorities for Annotation

Our ultimate aim is to provide comprehensive GO annotation for all gene products in each of the reference genomes. This is a huge task and requires us the prioritise the targets for curation. Our intial annotation efforts (Aug 20076- Sept 2007) focussed on orthologs of human disease genes but in Oct 2007 we widened our list to four priority areas:

  • Orthologs of human disease genes
  • Topical or ‘hot’ genes
  • Genes conserved from E. coli to human that currently lack GO annotation
  • Genes involved in (metabolic?) pathway

Each month we curate 5 genes from each area as selected by one of the participating databases.

Overview of project strategy

Every month each database curates the same set of 20 genes from our priority list (link to how we choose these). Working on the same genes together promotes discussion about annotations across groups and frequently leads to new terms being added to the gene ontology.

Curation process summary:

  • Where they exist, identify the ortholog(s)/homolog(s) of the selected target genes in each species - at present each database uses their own criteria to decide which orthologous/homologous genes to curate [include link to these?? on a separate page. Note they are not in a standard format at present but could maybe be summarised - if we decide to include these then each group should review content to make sure it is ok for the public site - I know mine is a bit informal at present] but we are investigating a standardised approach.
  • Enter the gene identifiers in a shared spreadsheet so that all curators can see the set of genes being curated
  • Collect available literature about the genes
  • Assign GO terms based on experimental data
  • Review existing GO annotations to make sure they conforms to agreed standards [link to relevant section]
  • Record in shared spreadsheet that GO annotation when is considered comprehensive for each gene [link to relevant section].

How does this project differ from standard GO annotation?

The reference genome databases have agreed to follow guidelines that are more stringent than those used for standard annotation:

  • Experimental evidence codes (IDA, IMP, IGI, IPI, IEP) should be used where possible
  • Terms inferred from sequence and structural similarity (ISS) should only be used where the terms are supported by experimental evidence for the similar sequence
  • Non-traceable author statements (NAS) should be avoided
  • No new annotations should be based on traceable author statements (TAS); existing terms assigned with TAS should gradually be replaced with the appropriate experimental evidence code based on the primary literature

How do we know when GO annotation is comprehensive?

The amount of literature per gene is very variable. Where possible we review every paper about a given gene and capture all possible GO terms but this is only feasible when there are tens of papers. For genes associated with hundreds or even thousands of publications we cannot read all of the papers so we do our best to prioritise the literature and capture all aspects of gene with GO terms. In this situation we often work from recent reviews to lead us to key experimental papers. If you think we have failed to capture some aspect of your favorite gene then please let us know [go help - or do we need a separate form?].

In some cases, there is no experimental data for any of the reference genome species but experimental data may be available in other model systems; in these cases we submit GO annotations for the relevant species to GOA [link] so that this information is captured from the primary literature.

Where can GO annotations from the project be viewed?

All GO annotations from this project are included in the [gene association files] that each group submits to GO and can be viewed using [AmiGO].

It is also possible to view the annotations for each annotated gene. A colorful graphic representation of the reference genome effort can be viewed in full here:
http://www.geneontology.org/images/RefGenomeGraphs/

There is one graph per curated reference gene. In addition to the graph each page includes two informative tables, which either lists GO annotations by broad GO category (GO slim), or shows full experimental annotations in each organism for the given gene. This facilitates comparison of the curation status in the 12 reference genomes and helps curators to identify genes that need attention.

POLAgraph.png Partial Graph of Gene POLA

Activities

(this is probably not necessary?)

  • Monthly Conference Calls
  • First Reference Genome Annotation Meeting, Princeton, NJ, Sept 26, 27, 2007