NEW YORK (GenomeWeb) – A million genomes could be accessible to European researchers within the next few years thanks to a new pan-European effort to pool genomic data. Seventeen European countries have signed a declaration to have a million genomes sequenced and shareable by 2022.
Croatia, the latest country to join the effort, signed the declaration last week. Other countries that have signed on to the project include Austria, Bulgaria, the Czech Republic, Cyprus, Estonia, Finland, Greece, Italy, Lithuania, Luxembourg, Malta, Portugal, Slovenia, Spain, Sweden, and the UK.
Signatories have promised to deliver cross-border access to a genomic database, which they hope will swell beyond the million genomes mark in the future, providing the scale for researchers to make new clinically significant associations in research. Under the agreement, they aim to create a governance model for cooperation, support the technical capabilities to ensure data sharing, and facilitate interoperability of the registries and databases to support research.
Representatives of signatory countries met last week in Brussels to discuss funding and how to best reach the target of making a million European genomes accessible in four years, as well as to assess the infrastructure, legal, and ethical requirements to facilitate secure data access. It was the first time representatives of participating countries have met since they announced the effort in April.
"There is a real opportunity for Europe here that we must grab," said Niklas Blomberg, director of ELIXIR, which sees the new project, called the Million European Genomes Alliance, as being in line with his organization's mandate to coordinate life sciences resources across Europe. ELIXIR is headquartered at the Wellcome Trust Campus in Hinxton, UK, and Blomberg has played an active role in debating the future of the initiative.
"The weakness of Europe is that it is fragmented into many countries, meaning that it's difficult to achieve the transformative scale of genome science within any country in Europe," Blomberg said. However, should Europe succeed in establishing the framework for sharing genomic data, it could serve as a model for other countries and regions. "There are many countries in the world with strong national genome projects that can't achieve scale," he said. "If we can show the way forward, it will be the starter for [data] federation. That is a real opportunity."
Achieving that, however, will take financial support from the European Commission, which, by supporting the new declaration, has shown the political will to make it happen. Denis Horgan, executive director of the European Alliance for Personalized Medicine, a Brussels-based nonprofit, has been lobbying the EC as well as member states to take the lead in such an alliance for years.
"The idea of MEGA was to have an overarching idea for Europe, to have different efforts to bring genomics-based medicine into the healthcare system," Horgan said. "The idea was not sequencing per se, the idea was how could you get member states to work on a common effort," he said.
It was also inspired, in part, by the Precision Medicine Initiative in the US, which also aims to build a research cohort of at least a million individuals that will include their genomic data.
"They would like to do it because the Americans are doing it," said Andres Metspalu, director of the Estonian Genome Center in Tartu, which will participate in the project. "The Europeans don't want to get left behind," he said. "So, there are political motivations and medical motivations."
While the April declaration was the fulfillment of EAPM's quest to have the European Commission get behind the dream of a million accessible genomes in Europe, Horgan noted that the declaration and the first meeting held this month are merely the start of an effort that faces major challenges, including a lack of data harmonization, common standards, interoperability, and even fragmentation at the domestic level, as different regions within participating member states have different projects underway.
"A key area for us going forward, as a nonprofit, is to help to develop a governance framework" around the project, said Horgan. "That will be a theme for the next few years."
Blomberg predicted that MEGA will be a federated project, coordinated by multiple actors, that allows clinicians to access genomes stored in each country "via some sort of cloud associated with that data source."
This will differ from the approaches of previous international collaborations, such as pan-cancer data-pooling efforts, where data was collected and stored in a single database. Enabling access in this way, though, will "hinge on implementing strong standards" in signatory countries, said Blomberg. While acknowledging the challenge, Blomberg expressed optimism that it was achievable by the initiative's projected completion date of 2022, consolidating in one resource a mass of data that has not existed to date.
"We could conceivably relatively soon in Europe ... have a large collection of national reference cohorts that taken together have a very diverse view of genomics," Blomberg said.
It's a new way of doing things for European scientists, who are accustomed to sharing data within smaller communities aligned with research interests, often led by one or several principal investigators. "It would be a mistake to think about [MEGA] the same way we think about the Human Genome Project or Human Cell Atlas, with one strong scientist at the helm," Blomberg said. Rather, MEGA participants will look to the European Commission to support a "portfolio grants" via funding instruments such as Horizon 2020 or Horizon Europe over time to carry out the sequencing and build the infrastructure to realize the aims of the project. "It will require a lot of different organizations including ELIXIR working together to make this happen," said Blomberg.
For Ivo Gut, director of the Centro Nacional de Análisis Genómico (CNAG) in Barcelona, pursuing MEGA via a federated system would be "quite smart," though it would require participants to decide on standards, organizations, operating languages, and the like. "It's all manageable," Gut said, "but it will require discussion on how to do it."
Gut, who has also taken on an active role in fleshing out the details of the initiative, said that the effort was necessary to overcome the smaller scale of various national and regional genome projects in Europe. MEGA will allow European researchers to "get more bang out of what everyone is doing," allowing scientists, such as those studying rare diseases, to access content that could help them move beyond the paradigm of identifying rare mutations in single patients.
"If you see it once, it's an anecdote, and if you see it twice, you might start worrying about it," noted Gut. "But, if you see it 50 times, twice in every member state, then you might think it's a real effect and you might start doing something about it," he said. "To me that is the motivator for a project such as MEGA."
Like Blomberg, Gut said that the European Commission will play a "pivotal role" in providing the resources for accomplishing MEGA's goals. At the same time, he doesn't believe the European Commission will, say, spend the money to sequence a million genomes outright.
Rather, once the infrastructure is in place, getting to a million genomes will be incremental, relying both on EU and member state budgets.
It will also depend on the participation of larger countries, such as France and Germany, that so far have not signed on to the declaration. As part of its Médecine Génomique 2025 project, France has sought to create a network of centers that will be able to produce 235,000 genomes annually by 2020, for instance, a large potential source of data for MEGA.
"Genomics England has about 70,000 whole genomes, and the whole of Europe has maybe 100,000 all together," noted Gut. "Once these initiatives, like the French initiative, get operational and start running, then we'll get closer."
Within CNAG, Gut has also spearheaded the creation of an integrated platform for rare diseases research called RD-Connect. He noted the similarities between RD-Connect and the envisioned MEGA data-sharing capabilities, and suggested that RD-Connect could become a solution to underlie a federated data-sharing system. "We are looking at other countries picking up RD-Connect as a container for their data."
Once the infrastructure is in place, though, there is no reason why MEGA should stop at one million genomes, Gut added. "Considering that there are about 350 million Europeans, a million genomes is just a drop in the bucket," he said.
The Estonian Genome Center's Metspalu agreed. "Of course, a million is not enough for Europe," he said. "I propose that we have to sequence at least five million."
But whether it's one million or five million, it will ultimately be the European Commission and member states that will determine when the initiative hits those numbers. "The time frame sits in the hands of the funders," said Blomberg. "But I believe it will happen sooner rather than later."