Across the world, many laboratories are conducting research relating to the SARS-CoV-2 virus, whether it be to understand the pathophysiology of COVID-19, or to develop robust diagnostics and efficacious therapeutics for the disease. As such, the pandemic has highlighted the critical importance of data sharing within the scientific community.
The iReceptor Plus consortium, a European Union (EU)- and Canadian-funded project, has gathered 200 million T and B cell receptor sequences from COVID-19 patients – it is the largest repertoire of its kind. The sequencing data is open source and available online through the iReceptor Gateway.
In an exclusive interview, Technology Networks spoke with Felix Breden, scientific manager at iReceptor Plus, to learn more about the Gateway, and the various ways the sequencing data might be used to aid vaccine design and our understanding of clinical variability in COVID-19 patients.
Molly Campbell (MC): Can you tell us about the rationale behind creating the iReceptor Plus consortium? What are the consortium’s aims and who is involved?
Felix Breden (FB): The iReceptor Plus Consortium was formed in answer to a Canadian/EU collaborative grant program for increased data sharing in health and genomics. The aim is to continue the development of a Scientific Gateway – iReceptor Gateway – that was developed in Canada at Simon Fraser University starting in 2013.
The EU and the Canadian government have awarded €8.4 million to the internationaliReceptor Plus Consortium. The funding provided to the four-year project includes €7.85 million from the EU through the Horizon 2020 Research and Innovation Programme, and an additional C$800,000 from the Canadian government.
The aim is to facilitate sharing the enormous antibody/B cell and T cell receptor repertoires produced by the adaptive immune system that are critical to all aspects of modern immunotherapy: vaccine development, autoimmune disease therapy and novel cancer immunotherapy.
The adaptive immune system must be immensely diverse to detect all the pathogens an individual will encounter in its lifetime, including novel pathogens such as SARS-CoV-2. These immense datasets demand novel analysis tools and databases to curate, analyze and share these data.
The Consortium includes 19 participating institutions from nine countries, including academia, biopharma,clinics and hospitals.
MC: Can you discuss how the 200 million T and B cell receptor sequences were obtained? Were they any challenges related to collecting this data?
FB: The Gateway at present curates almost 200 million T and B cell receptor sequences from COVID-19 studies. One of the most exciting developments with these studies is that researchers are reaching out to the Consortium to share their data through the Gateway; the community has really responded and is willing to share their data even before their papers are accepted. This shows a growing commitment to share data for the common good in a data commons.
Laura Lansdowne (LL): What can the sequence data tell us about SARS-CoV-2 and the immune response?
FB: The data can show for example what antibody/B cell clones are greatly expanded in a patient with COVID-19; the expanded clones are presumably those that are best at binding to the SARS-CoV-2 virus. The sequence from any of these expanded clones can then serve as a possible candidate for a vaccine, where the immunogenetic sequence is engineered into a “dead” virus, in the hope that the original sequence will induce antibodies in a naïve person.
Also, the genes that produce antibodies and T cell receptors are highly variable within and between individuals and populations. Understanding what genes are expressed to encode antibodies that can neutralize (defeat) the virus can determine if population specific vaccines are necessary, and again reinforce which are good vaccine targets from among the many responses to the virus that researchers are observing.
MC: How might this data be used to develop anti-COVID-19 diagnostics, therapeutics and vaccines?
FB: It is important to understand that the iReceptor Scientific Gateway's biggest function is to allow comparisons among studies. One study may show that half of the patients had a certain type of clone expanded in severe COVID-19 cases, but this might be a sample of only 100 individuals. By allowing comparisons among many labs and institutions, it is possible to see how statistically valid the patterns that are seen in only one study are, versus those that are observed in multiple studies from multiple researchers. That is why we are working so hard to get as many studies as we can curated from COVID-19 patients through the Gateway.
LL: How can researchers join the consortium so that they are able to share and access the data?
FB: The Gateway is open source and the data are publicly accessible. Researchers can contact firstname.lastname@example.org to obtain an account to search and download data, or to discuss with the iReceptor team how to make their COVID-19 patient data available through the Gateway.
LL: The iReceptor Gateway goes beyond just COVID-19 data, could you touch on the other disease datasets included?
FB: The Goal of the Consortium is to integrate studies from all types of diseases that involve the adaptive immune system: infectious diseases (HIV, COVID-19, influenza), autoimmune diseases (multiple sclerosis, lupus) and cancer (melanoma, ovarian, etc.). Understanding the similarities and differences among the responses to these various diseases can lead to new diagnostics and therapeutics.
Felix Breden was speaking to Molly Campbell and Laura Elizabeth Lansdowne, Science Writers for Technology Networks.