GA4GH Genomic Knowledge Standards Work Stream welcomes new Co-Leads Melissa Cline and Alex Wagner

29 Aug 2024

Melissa Cline, of the University of California, Santa Cruz, and Alex Wagner, of Nationwide Children’s Hospital, have been appointed as the new Co-Leads of the GA4GH Genomic Knowledge Standards (GKS) Work Stream.

By Jaclyn Estrin, GA4GH Science Writer

The Global Alliance for Genomics and Health (GA4GH) is pleased to welcome Melissa Cline of the University of California, Santa Cruz, and Alex Wagner, of Nationwide Children’s Hospital, as the new Co-Leads of the Genomic Knowledge Standards (GKS) Work Stream.

Genomic knowledge originates from the study of an individual’s genome — all the DNA in one’s body — and the accompanying biomedical information inherent within it.

If a patient is suspected to have a genetic disease — one that results from an abnormality in one’s DNA — doctors may study that person’s genome to explore whether genetic differences, also known as variants, are present and a possible cause of the disease.

Because each person possesses nearly five million variants, clinicians have the challenging task of pinpointing the specific variant that might cause the genetic disease. Computer searches are also limited by the absence of a common language to describe variants of clinical importance. 

The GKS Work Stream strives to enable communication among computers by developing a standardised language to describe genetic variants and their attributes. This will facilitate the secure search, exchange, and application of genomic knowledge to promote greater understanding of genetic diseases and advance patient care.

Previously under the lead of Robert Freimuth (Mayo Clinic) and Andy Yates (EMBL’s European Bioinformatics Institute), the GKS Work Stream has an active and engaged contributor base driving the standards forward. Cline and Wagner now take the helm and are looking forward to building off the momentum the Work Stream has cultivated to date.

Wagner is a principal investigator at the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital. His research interests focus on sharing and harmonising genomic data, particularly in the cancer field. He works to advance precision medicine and garner a greater understanding of genomic cancer variants by standardising their representation and annotation. His first involvement with GA4GH was through engagement with the Variant Interpretation for Cancer Consortium (VICC) Driver Project, which aims to advance precision oncology through a coordinated effort to share standardised information about cancer variants. 

Wagner quickly became involved in the GKS Work Stream, where he worked with Reece Hart (MyOme) and Larry Babb (Broad Institute of MIT and Harvard) to drive the Variation Representation Specification (VRS) v1.0 through its first product approval. He is now a Product Lead for VRS, a standardised computational language designed to facilitate reliable and secure exchange of genetic variation information among global institutions, labs, and systems. He also engages in the GA4GH Cancer Community, where knowledge is shared about utilising GA4GH standards to enhance oncology care.

Cline, a longstanding contributor of GA4GH for nearly a decade, has a scientific career focused on genomic data sharing. She has shared her expertise with GA4GH as an active participant of GKS, also supporting the development of VRS. In addition, she previously served as a Product Steering Committee member through her leadership role with the BRCA Challenge, one of GA4GH’s first Driver Projects.

At the University of California, Santa Cruz, Cline is the Program Manager for BRCA Exchange, the primary output of the BRCA Challenge and a global repository of BRCA1 and BRCA2 variants. The BRCA Exchange is designed to enable responsible data sharing to support researchers and health professionals in gaining a deeper understanding of BRCA variants and the genetic roots of breast, ovarian, and pancreatic cancer, along with other diseases.

Wagner and Cline have both expressed their excitement in working with each other and addressing several key priority areas to encourage the continued growth of the Work Stream. Together, they aim to engage stakeholders throughout the GA4GH community in implementing GKS products. By building off of the successful implementations of VRS by a few core Driver Projects, the Co-Leads want to engage a broader set of implementers to advance uptake of all GKS products.

Cline noted a priority of fostering cross-Work-Stream collaboration. “GA4GH has been effective in laying the groundwork for community driven standards,” Cline said. “GA4GH has also been effective at getting a diversity of stakeholders to the table to collaborate together on the definition of those standards.”

“One of my goals is to think about how we can facilitate broader perspectives and engagement in the Work Stream,” Wagner said. In this way, GA4GH can bring together a group of community members to build products that are “transparent, open, consensus-based, and FAIR [Findable, Accessible, Interoperable, and Reusable].”

Another goal is to define clear procedures to operationalise standards development activities. This would involve leveraging the expertise and experience of the active contributor base to formalise lessons learned, outline a process for new participants to carry the work forward, and consider a phased approach to implementation at a larger scale.

Cline emphasised this vision by saying, “I hope to see the point when some of the GKS products are so commonly adopted that the people forget that they’re GA4GH products.” This suggests a future state in which GKS products are so ubiquitous and widely implemented that they take on a life of their own even outside of the sphere of GA4GH.

Wagner agreed, “I am most excited about the potential to get over what have been long-standing challenges in the field through the advancement and adoption of these genomic knowledge standards.”

Cline and Wagner expressed that sharing genomic knowledge requires community-driven standards. The Co-Leads, along with active GKS contributors, are working to enable the genomic knowledge exchange that is key to advancing research, unlocking the potential of precision healthcare, and improving human health outcomes.