title: Improving the Sequence Ontology terminology for genomic variant annotation.
abstract: BACKGROUND
  The Genome Variant Format (GVF) uses the Sequence Ontology (SO) to enable detailed annotation of sequence variation. The annotation includes SO terms for the type of sequence alteration, the genomic features that are changed and the effect of the alteration. The SO maintains and updates the specification and provides the underlying ontologicial structure.
  
  
  METHODS
  A requirements analysis was undertaken to gather terms missing in the SO release at the time, but needed to adequately describe the effects of sequence alteration on a set of variant genomic annotations. We have extended and remodeled the SO to include and define all terms that describe the effect of variation upon reference genomic features in the Ensembl variation databases.
  
  
  RESULTS
  The new terminology was used to annotate the human reference genome with a set of variants from both COSMIC and dbSNP. A GVF file containing 170,853 sequence alterations was generated using the SO terminology to annotate the kinds of alteration, the effect of the alteration and the reference feature changed. There are four kinds of alteration and 24 kinds of effect seen in this dataset. (Ensembl Variation annotates 34 different SO consequence terms: http://www.ensembl.org/info/docs/variation/predicted_data.html).
  
  
  CONCLUSIONS
  We explain the updates to the Sequence Ontology to describe the effect of variation on existing reference features. We have provided a set of annotations using this terminology, and the well defined GVF specification. We have also provided a provisional exploration of this large annotation dataset.
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Cunningham
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Moore
authors.affiliation: Department of Biomedical Informatics, University of Utah, Salt Lake City, UT USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ruiz-Schultz
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD UK ; Wellcome Trust Sanger Institute, Hinxton, Cambridge UK.
authors.forename: Graham Rs
authors.initials: GR
authors.lastname: Ritchie
authors.affiliation: Department of Biomedical Informatics, University of Utah, Salt Lake City, UT USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Eilbeck