The VEP’s caches are built for each of Ensembl’s primary species (70 species as of Ensembl version 84); the files are updated in concert with Ensembl’s release cycle, ensuring access to the latest annotation data. Cache files for all previous releases remain available on Ensembl’s FTP archive site [91 ] to facilitate reproducibility. For 15 of these species there are three types of cache files: one with the Ensembl transcripts, a “refseq” one with the RefSeq transcripts, and a “merged” one that contains both. Caches for both the latest GRCh38 and previous GRCh37 (hg19) human genome builds are maintained. The human GRCh38 cache file is around 5 gigabytes in size, including transcript, regulatory, and variant annotations as well as pathogenicity algorithm predictions. Performance using the cache is substantially faster than using the database; analyzing a small VCF file of 175 variants takes 5 seconds using the cache versus 40 seconds using the public Ensembl variation database over a local network (performance can be expected to be slower when using a remote database connection).
The VEP can use FASTA format files of genomic sequence for sequence retrieval. This functionality is needed to generate HGVS notations and to quality check input variants against the reference genome. The VEP uses either an htslib-based indexer [92 ] or BioPerl’s FASTA DB interface to provide fast random access to a whole genome FASTA file. Sequence may alternatively be retrieved from an Ensembl core database, with corresponding performance penalties.
Cache and FASTA files are automatically downloaded and set up using the VEP package’s installer script, which utilizes checksums to ensure the integrity of downloaded files. The installer script can also download plugins by consulting a registry. The VEP package also includes a script, gtf2vep.pl, to build custom cache files. This requires a local GFF or general transfer format (GTF) file that describes transcript structures and a FASTA file of the genomic sequence.
The VEP can use FASTA format files of genomic sequence for sequence retrieval. This functionality is needed to generate HGVS notations and to quality check input variants against the reference genome. The VEP uses either an htslib-based indexer [92 ] or BioPerl’s FASTA DB interface to provide fast random access to a whole genome FASTA file. Sequence may alternatively be retrieved from an Ensembl core database, with corresponding performance penalties.
Cache and FASTA files are automatically downloaded and set up using the VEP package’s installer script, which utilizes checksums to ensure the integrity of downloaded files. The installer script can also download plugins by consulting a registry. The VEP package also includes a script, gtf2vep.pl, to build custom cache files. This requires a local GFF or general transfer format (GTF) file that describes transcript structures and a FASTA file of the genomic sequence.
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