ga4gh.org
GKS: the Fellowship of the VRS
Andreas Prlic & Larry Babb (and Alex Wagner)
ga4gh.org
Agenda (draft)
ga4gh.org
VRS Greatest Hits
Notable Features
Ref. Allele Guidance
Gen. Normalization
Release Cycle
VMC
1.0
Notable Classes
Allele
Text Variation
SequenceLocation
SequenceState
SimpleInterval
Notable Features
Terminology
Information Model
Schema
VOCA Normalize
VRS-Python
Notable Features
Systemic Variation
Molecular Variation
Primitive Constraints
GA4GH Domain Docs
1.1
1.2
October 2019
September 2020
July 2021
May 2016
VR
October 2017
GKS and the Variation Representation Team is announced at the 5th GA4GH Plenary
The Variant Model Collaboration is formed to model Variation as semantically-linked value objects
1.3
Notable Classes
ChromosomeLocation
CytobandInterval
Haplotype
VariationSet
Notable Classes
SequenceExpressions
Gene (&Features)
CopyNumber
April 2023
Notable Classes
Genotype
CopyNumberCount
CopyNumberChange
Notable Features
PGx Diplotype
Improved CNVs
ga4gh.org
VRS: a Genomic Knowledge Standard
Copy Number Count
Copy Number Change
Genotype
Pugh T, et al. Genetics in Medicine (2015)
Goar W, et al. Pacific Symposium On Biocomputing (2023)
ga4gh.org
VRS v1.3 at scale: gnomAD
Added VRS for all 759.3 million variants in gnomAD v3 Hail Tables, plus reference alleles.�Over 1.5 billion VRS v1.3 Alleles, now searchable by range and computed identifier.
ga4gh.org
Contextualizing evidence with VRS: MaveDB
Arbesfeld J, et al. bioRxiv (2023)
ga4gh.org
Contextualizing evidence with VRS: MaveDB
ga4gh.org
A Glimpse of the Future: GK-Pilot v2
2022 GA4GH 10th Plenary: Genomic Knowledge Pilot (GK-Pilot) v1
Recap
ga4gh.org
A Glimpse of the Future: GK-Pilot v2
GK-Pilot v2 Enhancements
Uses VRS 2.0-alpha
Uses Categorical Variation
Extends the VA Statement model
ga4gh.org
Maturity Model Today
Level | Criteria | Schema Changes | Support |
Alpha | A requirements survey has been done and an information model (IM) drafted. The IM has been realized as a technical schema. | Expected frequently. Not permitted in pre-release / release branches. | IM and technical schema are produced and made publicly available. |
Beta | Alpha + the technical schema has been used to generate messages in a test system, and a validation framework applied to ensure specification conformance. Documentation has been generated and is publicly accessible. | Expected infrequently. Only permitted in beta release branches. Notifications sent to the GKS VR team. | Alpha + test system data, validation framework, and documentation are made publicly available. |
Release Candidate | Beta + the data class is sufficient for multiple data providers. Inter-system interoperability has been demonstrated. Data class is considered ready for broad adoption and testing. | Expected rarely. Only permitted in beta and release candidate branches. Changes in consultation with registered adopters. | Beta + reference implementation tools are published |
Stable | Release Candidate + Data class has been sufficiently tested to warrant long-term support from the specification maintainers. | Breaking changes will not occur within any branch of a major version once stable. | Release Candidate + major version minted. The data class will be fully supported by all spec maintainer tools until 2 years following the next major version release. |
ga4gh.org
Repo Branch Structure and Data Class Maturity
Feature Branches
(Alpha Maturity)
Pre-Release Branches
(Beta / RC Maturity)
Release Branches
(Stable Maturity)
ga4gh.org
Main Event: VRS 2.0 alpha: Key Changes (focused discussions)
ga4gh.org
VRS 2a: No more ValueObjectDescriptors!
Optional fields allowed on VRS objects
Modified "Digest" algorithm to understand "required" attributes
Every object has an optional "digest" attribute
The right attribute in the right place (for nested and referenced objects)
ga4gh.org
Resource identifiers (no more CURIE?)
Identified need for more direct method for referenceable objects in json
Investigated FHIRs solution
Proposing use of JSON schema uri/iri-reference for Resource identifiers
ga4gh.org
VRS 2a: New! SequenceReference Class
This is the "special" bridge to coordinating with the RefGet SQ id
To represent Sequences in VRS we need to use SQ.<digest>
We also need the control to decorate and reference the Sequence
SQR is our solution
ga4gh.org
VRS 2a: New! ReferenceLengthExpression State
ga4gh.org
VRS 2a: Re-thinking (non-identifiable) Text Variants
The Utility Variation concepts in VRS 1.x
VariationSet
Text
To our knowledge these have not materialized to be useful
Text Variation is nonsense as an identifiable VRS variation
But we need to handle situations these use cases
DescribedVariation is a CategoricalVariation concept to replace Text.
ga4gh.org
SV SIG & Categorical Variation Plans
Active Initiative: � Structural Variation
Upcoming Initiative: � Categorical Variation
ga4gh.org
Categorical Variation
Categorical variant
Examples:
ga4gh.org
Categorical Variation - Problem
Want to better support this in future. (VRS, MetaKB, etc)
ga4gh.org
Categorical Variation
ga4gh.org
Categorical Variation - Typology in CIViC
ga4gh.org
ClinVar & CIViC GK-Pilot v2 alpha Introduction
prep for next session!
ga4gh.org
ClinVar GK-Pilot Statement Walkthrough
ga4gh.org