7 February 2023
A GA4GH group that tackles the problem of representing structural variations in sequenced DNA is seeking members. (Interested? Complete a brief form.)
In 2019, the GA4GH Genomic Knowledge Standards (GKS) Work Stream released the Variation Representation Specification (VRS), a standard that offers a flexible framework of computational models, schemas, and algorithms to precisely and consistently exchange genetic variation data across different fields and user communities. (For instance, pharmacogenomics researchers may describe genetic variants differently than mendelian disease clinicians do.)
The specification significantly reduces ambiguity when exchanging variation data. This makes the clinical annotations that are central to personalised medicine much more reliable and useful.
VRS was deliberately designed as an extensible model that can precisely and computably capture standard computational data structures for basic biological concepts, such as “allele,” “sequence,” and “genotype.” The specification also reflects more complex descriptions of biological variation, such as haplotypes, and copy number variation models.
A category of variation of particular interest to the Variation Representation team is the broader class of structural variation. Often described as rearrangements of large segments of DNA, structural variations can have a significant impact on human disease. They are also notoriously difficult to resolve using short-read sequencing technology. And no matter what sequencing technology you use, they are challenging to represent. This stems partly from the fact that structural variations tend to occur in large genomic regions that are highly repetitive and highly variable from one person to the next.
To tackle this challenge, and achieve the long-standing goal of incorporating structural variations into VRS, the GKS Work Stream is convening clinicians, bioinformaticians, electronic health record vendors, researchers, testing laboratory representatives, genomic-knowledge-base maintainers, and anyone else involved in the reporting and exchange of patient genomic data in a Special Interest Group focused on structural variation. The group will undertake a time-limited effort to standardise structural variation modelling and development. It will cover fusions, rearrangements, and other classes as selected by group members.
The Special Interest Group will aim to develop a VRS model and schema for representing structural variations discretely and computably. To accomplish this, they will identify and review structural variation concepts from disparate use cases. The Special Interest Group will use this landscape analysis to define the scope and models for concepts supporting structural variations — including breakpoint coordinates, exon/intron identification, transcript junctions, segment phasing, impacted genes, and (de)composition of complex variants.
If you are interested in participating in the new VRS Special Interest Group focused on structural variation, complete this form. With broad representation of expertise and experience, the GKS Work Stream hopes to effectively and efficiently work through this crucial challenge.