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iReceptor Plus Consortium Wants to Improve Immunological Data Sharing

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CHICAGO (GenomeWeb) – The nascent iReceptor Plus Consortium, funded by €8.4 million (about $9.6 million) in awards from the European Union and the Canadian government, has the broad mandate of promoting integration and sharing of human immunological data. The hope is that the four-year effort will yield better understanding of immune responses and lead to new therapeutic targets for drug developers and clinicians.

As previously reported, the funding will support development of a technology platform to integrate distributed repositories of Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) data, which is intended to improve precision medicine and immunotherapy in cancer, inflammatory and autoimmune diseases, allergies, and infectious diseases.

This is one of six projects involving distributed sharing of omics data from a joint call put out by the EU and the Canadian Institutes of Health Research last year. "The selected projects should build on the data quality metrics, standards, and access policies developed by major international initiatives," according to the official announcements.

Immunogenomics looks at T-cell receptor and B-cell receptors. "iReceptor Plus is a project that is aimed at better integrating ... massive datasets made of TCR and BCR sequences," said consortium member David Klatzmann, chief of biotherapy at Pierre and Marie Curie Medical School and Pitié-Salpêtrière Hospital in Paris.

The consortium initially includes about 20 partners, mostly from the EU, though four are from North America: Simon Fraser University and the University of Toronto in Canada, plus the University of Texas Southwestern Medical School and 10X Genomics in the US. Leaders wanted to include academic, industry, and clinical partners, according to iReceptor Plus Coordinator Gur Yaari of Bar-Ilan University in Israel.

"The idea is that throughout this grant, the clinical partners will be more and more involved because they will open their own nodes in this network and can utilize whatever we are building," Yaari said.

Specifically what they are building has yet to be determined, though there are some guidelines and blueprints in place. The network must follow the principle set forth in the agreements with the EU and Canada that the network be distributed in order to break down barriers that have hindered data sharing in the past.

"This field is tightly connected with confidentiality," Yaari said. Companies involved in immunogenomics tend to sequence plenty of immune repertoires, but, since many are involved in drug development, they keep the data to themselves, according to Yaari.

The iReceptor Plus Consortium is building on work of the AIRR community. "We know which defined standards to use for databases, and so on," Yaari said.

The initial plan is for each participant to have its own databases. "We will develop [application provider interfaces] and communication protocols that will allow you to collectively decide what part of the data you want to share and with whom," Yaari explained.

Bar-Ilan University is working on "some kind of turnkey system" that hospitals can just connect to their databases and convert TCR and BCR data into an iReceptor Plus-compatible format, he said.

"We also will have some kind of gateway, which will have user interface and visualization tools and simple analysis tools that will allow people to ask metadata questions and to have meta-analysis," Yaari said

For example a user could go to the gateway to query the network in search of V-gene distribution for patients with multiple sclerosis. "Whoever wants to share this information will send it back according to a uniform standard, and then meta-analysis will be much easier and much more accessible," Yaari said.

Klatzmann wants to be able to search for sequences that are relevant to sequences he generates in his lab in Paris. "In order to do this, you have to establish a system that will allow you to query databases that have not been created in the exact same format," he said.

There also should be a way to get at the metadata associated with each sequence, including immunophenotyping, transcriptomics, and microbiomics.

"We have all these data that are then linked to the analyses of T-cell receptors from these patients, so it's important that you can actually not just look at the TCR sequence, but also to look at associated data," Klatzmann said. "For example, T-cells and microbiota have important interactions."

First, though, consortium members have to develop not only analysis tools, but the security and scalability necessary to support transfer of large amounts of sensitive data that researchers have been reluctant to share in the past.

"We call it scaling up and scaling out, which means many more nodes to the system," Yaari explained.

The consortium officially started Jan. 1 and held its kickoff conference Jan. 14-16 in Eilat, Israel. "The main goal of this conference was … establishing connections and establishing collaboration … so we will have concrete ideas of what to do next," Yaari said.

In that regard, the event was successful, he said, as the consortium is a complex set of partners who did not all previously know each other.

However, they have a lot of work to do because immunoreceptor informatics has not been as mapped out as other areas of genomics, particular in the clinical realm.

"We have our use cases of the research community which is quite well-established, but transferring it into the clinical partners, that's the new step," Yaari said.

One area that is emerging is single-cell immunology, which is one of the several "work packages" called for in the EU-Canada agreement, alongside systems immunology, machine learning, and others. "We want to add the capacity to handle single-cell data in this system," Yaari said.

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