Implementations¶
The libraries and applications listed below have implemented the GA4GH Variation Representation Specification to store and exchange variation data. They are listed here to demonstrate VR utility and as a resource for those considering implementing VR-Spec. These packages are not supported by GA4GH.
Libraries¶
Libraries facilitate the use of the VR-Spec, but do not implement a particular use or application. Although there is only one library currently, it is expected that others will eventually appear as VR-Spec is adopted.
vr-python: GA4GH VR Python Implementation¶
The GA4GH VR Python Implementation is an implementation for the GA4GH VR-Spec. It supports all types covered by the VR-Spec, implements Allele normalization and computed identifier generation, and provides “extra” features such as translation from HGVS, SPDI, and VCF formats. See vr-python notebooks for usage examples.
VR Specification MAY be used without using the Python implementation.
Applications and Web Services¶
Applications implement VR-Spec to support specific use cases. Projects known to implement VR-Spec are listed below. Descriptions are provided by the application authors.
ClinGen Allele Registry¶
ClinGen Allele Registry [1] provides identifiers for more than 900 million variants. Each identifier (canonical allele identifiers: CAIds) is an abstract concept which represents a group of identical variants based on alignment. Identifiers are retrievable irrespective of the reference sequence and normalization status.
As a Driver Project for GA4GH, ClinGen Allele Registry implements two standards: RefGet and VR in the first implementation.
The API endpoints that support data retrieval in this two key standards are summarized in the following table.
HOST: https//reg.clinicalgenome.org/
| API Path | Parameters | Response Format | Example | |
|---|---|---|---|---|
| RefGet | ||||
| [GET] /sequence/service-info | - | Refget v1.0.0 | /sequence/service-info | |
| [GET] /sequence/{id} | id => TRUNC512 digest for reference sequence | Refget v1.0.0 | /sequence/vYfm5TA_F-_BtIGjfzjGOj8b6IK5hCTx | |
| [GET] /sequence/{id}/metadata | id => TRUNC512 digest for reference sequence | Refget v1.0.0 | /sequence/vYfm5TA_F-_BtIGjfzjGOj8b6IK5hCTx/metadata | |
| VR | ||||
| [GET] /vrAllele?hgvs={hgvs} | hgvs => HGVS expression | VR v1.0 | /vrAllele?hgvs=NC_000007.14:g.55181320A>T /vrAllele?hgvs=NC_000007.14:g.55181220del |
Support for GA4GH refget and VR specs provided in ClinGen Allele Registry is independent from VR-Python. Support for this community standards is implemented in ClinGen Allele Registry through extension of code written in C++.
BRCA Exchange¶
BRCA Exchange [2] proposes an API endpoint which will share the variant list in VR JSON model. Behind the scenes, all variants will be represented according to VR specification, in a separate table of the BRCA Exchange database, and the contents of this table will be served by the BRCA Exchange API. A stand-alone executable will leverage these data to integrate the BRCA Exchange variant set with the ClinGen allele registry.
VICC Meta-knowledgebase¶
The Variant Interpretation for Cancer Consortium (VICC; https://cancervariants.org) has a collection of ~20K clinical interpretations associated with ~3,500 somatic variations and variation classes in a harmonized meta-knowledgebase [3] (see documentation at http://docs.cancervariants.org). Each interpretation is be linked to one or more variations or a variation class.
As a Driver Project for GA4GH, VICC is contributing to and/or adopting three GA4GH standards: VR, Variant Annotation (VA), and the Data Use Ontology (DUO). VICC supports queries on all VR computed identifiers at the searchAssociations endpoint (vicc-docs). Features associated with each interpretation are represented as VR-spec objects.
- Example queries:
- Allele: https://search.cancervariants.org/api/v1/associations?size=10&from=1&q=ga4gh:VA.mJbjSsW541oOsOtBoX36Mppr6hMjbjFr
- SequenceLocation: https://search.cancervariants.org/api/v1/associations?size=10&from=1&q=ga4gh:SL.gJeEs42k4qeXOKy9CJ515c0v2HTu8s4K
- Text: https://search.cancervariants.org/api/v1/associations?size=10&from=1&q=ga4gh:VT.9Wer7KrxALcPRDRGVKOEzf9ZEKZpOKK0
References:
| [1] | Pawliczek P, Patel RY, et al. ClinGen Allele Registry links information about genetic variants. Hum Mutat 11 (2018). doi:10.1002/humu.23637 |
| [2] | Cline, M.S., et al. BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2. PLoS Genet. 2018 Dec 26;14(12):e1007752. doi:10.1371/journal.pgen.1007752 |
| [3] | Wagner, A.H., et al. A harmonized meta-knowledgebase of clinical interpretations of cancer genomic variants. bioRxiv 366856 (2018). doi:10.1101/366856 |