Improving the Sequence Ontology terminology for genomic variant annotation

Area of Science:

• Genomics
• Bioinformatics
• Ontology Development

Background:

• The Genome Variant Format (GVF) relies on the Sequence Ontology (SO) for detailed annotation of sequence variations.
• SO terms describe alteration types, affected genomic features, and the impact of variations.
• The SO is responsible for maintaining and updating its specification and ontological structure.

Purpose of the Study:

• To address missing terms in the SO for adequately describing sequence alteration effects on genomic annotations.
• To extend and remodel the SO to define terms for variation effects on reference genomic features.
• To enhance the descriptive power of GVF for genomic variation data.

Main Methods:

• Conducted a requirements analysis to identify necessary SO terms.
• Extended and remodeled the Sequence Ontology to incorporate new terms.
• Applied the updated SO terminology to annotate genomic variations.

Main Results:

• The updated SO terminology was used to annotate the human reference genome with variants from COSMIC and dbSNP.
• A GVF file with 170,853 sequence alterations was generated, detailing alteration types, effects, and features.
• The dataset included four kinds of alteration and 24 kinds of effect, with Ensembl Variation annotating 34 SO consequence terms.

Conclusions:

• Updates to the Sequence Ontology effectively describe the effects of variation on reference genomic features.
• A comprehensive set of annotations using the updated SO and GVF specification was successfully generated.
• A preliminary exploration of this large annotation dataset was provided.