Understanding Annotations Updates

Updating the Annotation engine vs updating data sources

Background

Update to annotations can be broadly categorized into two categories:

• Annotation engine (Annotator) update
• Annotation data update

Understanding the nature of these two types of updates is key when it comes to updating annotation.

Annotator update

The annotator is the engine that contains logic for core annotations such as computing variant consequences, HGVS notations, mapped positions (e.g. CDNA, CDS, protein positions), detecting gene fusions, etc., and perform annotation lookups from external data sources such as dbSNP, gnomAD, ClinVar, OMIM, etc. also known as supplementary annotations (SA). Update to the annotator entails new features or bugfixes to the compute or lookup mechanism. This is completely independent of the data update such as updating dbSNP from v154 to v155. In other words, the same annotator can annotate with dbSNP v154 and dbSNP v155 when provided with the appropriate data files.

Data update

The annotator uses data from various sources (listed in Introduction). For example, gene models used for core annotations are obtained from RefSeq and Ensembl. Supplementary annotations come from various sources such as dbSNP, gnomAD, ClinVar, OMIM, etc. Any of these data can be updated without updating the annotator as long as the file formats are compatible.

Update scenarios

Let us look at a few update scenarios.

Requirement	What needs to be updated /added	Suggested action
New transcripts and gene symbols	Cache files from RefSeq and Ensembl	Run DataManager
Update ClinVar	ClinVar SA files	Run DataManager
New external annotation	New SA files required	Submit feature request
New annotation feature	Annotator	Submit feature request