This story has been updated to reflect Epic Systems' membership in GA4GH.
NEW YORK – In releasing a major update to its strategic roadmap last month, the Global Alliance for Genomics and Health (GA4GH) is, among other goals, looking to become more relevant in clinical genomics.
"We … are really concerned about making sure our standards are used in the real world, [that] they solve real problems," said GA4GH CEO Peter Goodhand.
The update is a roadmap for achieving GA4GH's three "community imperatives": aligning internal and external genomic data standards; offering better support for the implementation of technical standards in a variety of settings; and, in the words of Goodhand, "getting closer to clinical relevance" by engaging with healthcare organizations.
This is the first refresh of the strategic plan since GA4GH Inc. was formed as a not-for-profit corporation in Canada in 2020 after years of operating under an informal community structure. GA4GH first released a strategic plan in 2017 and articulated its three top-level priorities in the 2020 update.
"What this update really is about is better organization alignment, mechanisms, groups to deliver on those strategic imperatives," Goodhand said. "I'm going to characterize the [refreshed plan] as an evolution, but also putting some concrete actions in place so we can deliver on the previous one."
Goodhand noted that healthcare data sharing has been a decades-long struggle. "Even though we were heavily led and inspired by the work happening in research, … people … realized, if this was ever going to make a real difference, it had to get over into the clinic," he said.
There currently is an issue with expressing genotypes in electronic health records. GA4GH also has historically had little direct contact with EHR vendors, though that is improving.
Goodhand noted that Epic Systems has been participating in recent meetings, for example. The EHR vendor became an organizational member of GA4GH last summer, and Peter DeVault, Epic's VP of genomics and interoperability, has been personally involved. Another EHR company, Meditech, has also been in regular contact with GA4GH.
"There's still a ton of work to do, but I think if we can get more clinically driven driver projects, and if we can engage more with industry that's facing clinical environments, that's how we'll reach that domain," Goodhand said.
While GA4GH has evolved from a matrix of so-called driver projects and workstreams — use cases that set the direction of interoperability efforts — into a full-fledged standards organization since its founding 10 years ago, driver projects that provide cues for the organization's work are still central to its operations.
GA4GH currently has 24 driver projects — including the Human Phenotype Ontology — but has not added any since 2019. The alliance had rejected proposals for additional projects over the last four years, even though funding had run out for some existing projects. The strategic update allows for new projects and sets term limits on current ones.
"It was important that we open up that opportunity to the broader [genomics] community and to be able to bring in more voices on a more regular basis," said Angela Page, director of strategy and engagement for GA4GH and a leader of the effort to refresh the strategic plan. "If GA4GH really is going to be successful, we do need to have as many voices at the table as we can."
The updated strategy allows GA4GH to have an annual open call for new driver projects, and the organization asked sponsors of current driver projects to submit letters of intent by May 1 if they wanted to continue. Page said that GA4GH's external review board is now considering those proposals.
Page expects there to be 30 active driver projects at any given time, on staggered terms of about three years, so spots can open up each year. She called the schedule a logistical issue now, but not as pressing as broadening the number of participants.
"One of the priorities of the evaluation process of driver project applications is to get more clinical projects into the driver project cohort, because that is one of the strategic goals that was identified in 2020," Page added.
She said she would like to see a "multipronged approach to clinical engagement," noting that the decentralized US healthcare industry is so different from national-level programs in GA4GH such as Genome UK and Genomics Australia.
The updated plan also addresses interoperability and alignment of GA4GH standards with external specifications, but Page said that the alliance will also look to harmonize its own standards.
Standards and partnerships
Another key element of the strategic refresh is the creation of the GA4GH Implementation Forum, or GIF, which supersedes earlier efforts called the Federated Analysis Systems Project and the Genomics in Health Implementation Forum. Goodhand called this a more pragmatic approach to convening everything from national-level genomics programs to technology development to clinical implementation efforts.
A longstanding partnership with Elixir, the European life sciences infrastructure for biological information, provides a peek into the workings of the GIF.
GA4GH has been releasing standards since 2018, when it first published its Beacon, Workflow Execution Service (WES), Htsget, and Refget specifications as application programming interfaces (APIs). The Htsget API allows researchers to stream data without having to copy and transfer large files, while Refget helps users retrieve reference sequences.
Page noted that genomics software company DNAstack came together with Elixir and researchers from the US National Institutes of Health (NIH) to produce some real-world demonstrations of Beacon.
"That was such a successful project, but it was not scalable in the format that we were doing," Page explained. "What we're trying to do now with the GA4GH Implementation Forum is to follow that same model, which is use case-driven."
The three projects GIF participants are now looking at cover federated variant analysis, federated imputation, and distributed data access. "Part of the idea is both to demonstrate interoperability [using GA4GH standards] but also to identify challenges or insufficiencies of the standards, so that that learning can then go back into the standards development process," Page said.
Page said that GA4GH is also looking to engage with other standards bodies, so they can align their efforts and avoid duplication. Organizations like Health Level Seven International (HL7) are already deeply focused on EHR and other clinical data, and there are established standards like the Logical Observation Identifiers Names and Codes (LOINC) for laboratory results and Digital Imaging and Communications in Medicine (DICOM) for imaging.
She noted that the developers of Phenopackets, a standard for sharing disease and phenotype information for diagnosing and treating rare and hereditary diseases including cancer, worked within the informal framework of GA4GH before they sought and received formal recognition from the International Organization for Standardization (ISO).
The legal structure brought by the incorporation of GA4GH in 2020 gives the organization the ability to hold assets and enter into formal contracts. It also allows it to accept sponsorship funding from private entities and potentially to launch a grant program. However, Goodhand said that 95 percent of the work of the alliance takes place outside the umbrella of GA4GH Inc., thanks to funding from host institutions and more than 400 active contributors around the world.
The Elixir strategic partnership predates the incorporation, though. Page called it more of a handshake agreement than a formal legal contract.
"One of the important things that we put in the guidelines is that … the details of each strategic partnership will be worked out individually by the individual partners," Page said. "In some cases, it's very important that it not be a legal agreement, and in some cases, it actually maybe should be. We have that flexibility."
Goodhand said that GA4GH is looking for perhaps a half dozen strategic partnerships but did not offer additional details.
GA4GH continues to be supported by the Broad Institute, the Wellcome Sanger Institute, the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI), the Ontario Institute of Cancer Research (OICR), and a series of grants from sources including the Canadian Institutes of Health Research and the European Union's Horizon 2020 program. The Broad, Sanger, and OICR founded the alliance and initially provided all of its funding.
Neither the alliance nor GA4GH Inc. has any staff. The more than 20 people responsible for organizational operations technically work for the host institutions. Goodhand, a former president of OICR, remains on the payroll there, while Page is employed by the Broad.