Using GVF for Clinical Annotation of Personal Genomes

Accurately describing the contents of Next Generation Sequencing (NGS) results is vital to both research and clinical analysis of genomic data. Genomics and medicine use different, often incompatible terminologies and standards to describe sequence variants and their functional effects. This creates an information bottleneck that prevents efficient translation of genome scale nextgeneration sequence (NGS) information into the clinic. While the Variant Call Format (VCF) has met some of these challenges, with regards to describing the results of variant calling pipelines, it lacks the structure needed for detailed annotation of the consequences of sequence alterations. To incorporate genomic results into electronic health records (EHR), the results must also be defined in ways that are compatible with existing medical informatics systems. The Genome Variation Format (GVF) is an extension of the existing genome annotation format GFF3, which uses ontologies to capture the semantic nature of the information on sequence features. GVF uses the Sequence Ontology (SO) to define the type of sequence alteration, the genomic features that are changed and the effect of the change. We have extended and remodeled the Sequence Ontology to include and define more terms that describe the consequence of a variant upon genomic features in support of the Ensemble variation databases. GVF represents genome annotations for clinical applications using existing EHR standards as defined by the international standards consortium: Health Level 7. This means that GVF can describe the information that defines genetic tests, allowing seamless incorporation of genomic data into pre-existing EHR systems. Here we demonstrate the power of GVF to describe, to exchange, and to empower clinical interpretation of personal genome data through an extension of the GVF specification is called GVFClin. The Sequence Ontology Project maintains and updates the specification and provides the underlying structure that describes sequence features, sequence alterations and variant effects and their relationships to each other. The specification is available on the web at http://www.sequenceontology.org/resources/gvfclin.html.