New Collaborative Research Study Between nference and the NIH Identifies Which Mutations Enable Highly Transmissible Viruses, Like SARS-CoV-2, to Persist in Human Circulation

Published in PNAS Nexus, this study has the ability to impact future research and inform more proactive and sustainable pandemic preparedness

CAMBRIDGE, Mass.–(BUSINESS WIRE)–nference, an AI-driven health technology company, today announced a new research partnership following the publication of a study demonstrating the value of characterizing SARS-CoV-2 viral sequences using its newly introduced ‘Distinctiveness’ metric. In collaboration with the National Institutes of Health (NIH), the study, titled “Quantifying the immunological distinctiveness of emerging SARS-CoV-2 variants in the context of prior regional herd exposure,” was published in PNAS Nexus.

“With over 13 million SARS-CoV-2 genomes sequenced globally over the last two years, there is unprecedented data to decipher how competitive viral evolution produces fitter variants,” said Venky Soundararajan, co-founder and Chief Scientific Officer of nference. “There is limited knowledge of a genomic signature that is shared primarily by the sequential dominant variants, including Omicron sublineages like BA.1, BA.2.12.1 and BA.5. The insight uncovered by the study is quite timely to begin understanding how a virus like SARS-CoV-2 is managing to adapt its genome over time to persist in human circulation for years.”

Study authors examined and compared the amino-acid changes that have occurred in all SARS-CoV-2 genomes collected to date. Results showed that new sequences accumulate mutations, which make them distinct from other viral sequences that circulated previously within the same geographical region. The study provides the first compelling genomic signal for how highly transmissive and immuno-evasive variants, like Omicron and Delta, may be able to out-compete thousands of other circulating SARS-CoV-2 lineages to emerge as dominant variants of concern within a specific region. Sequences belonging to these variants of concern exhibited significantly higher values based on the newly introduced Distinctiveness metric when compared with other contemporary sequences of that same region.

Leveraging their experience in monitoring SARS-CoV-2 sequences, researchers from the NIH-led ACTIV Tracking Resistance and Coronavirus Evolution (TRACE) Working Group were able to label which parts of the viral sequence were specifically important to track with the Distinctiveness metric.

“This new approach for quantifying which adaptations impact the ability for a virus to evade immune-related treatments will aid our goal to accurately monitor new sequences of concern,” said Dr. Joseph Menetski, Vice President, Research Partnerships, and Foundation for the NIH lead for ACTIV TRACE. “Along with our new member, nference, the ACTIV TRACE initiative continues to provide actionable information to assist in monitoring and testing COVID-19 variants.”

This latest study by nference builds on a prolific COVID-19 research initiative that has resulted in a series of peer-reviewed publications, many of which are published in partnership with academic medical centers, health systems, pharmaceutical, medical device and diagnostics companies as well as government health agencies, including the ACTIV TRACE Working Group. These studies have revealed important molecular, clinical, and epidemiological characteristics of the SARS-CoV-2 viral lifecycle and the real-world impact of the COVID-19 vaccines.

About nference

Through its powerful technology platform and software, nference is transforming health care by making biomedical knowledge computable. Its partnership with Mayo Clinic has given nference an opportunity to synthesize more than 100 years of institutional knowledge, producing real-world evidence in real-time by converting large amounts of de-identified data into deep insights to advance discovery and development of diagnostics and therapeutics. Its proprietary AI-enabled software platform has been used to accelerate life sciences research, development, and clinical care in significant ways, including biomarker discovery and validation, real-world evidence generation leveraging real-world data, early disease detection, public health policy generation and validation, and more. nference is headquartered in Cambridge, Mass. Follow nference on LinkedIn and Twitter. Visit us at

About the National Institutes of Health (NIH)

NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

About ACTIV Tracking Resistance and Coronavirus Evolution (TRACE) Working Group

The ACTIV TRACE initiative aims to prioritize which viral variants should be studied to determine the effectiveness of vaccines and therapeutics currently in late stages of development against these variants; coordinate data sharing; and confirm testing and periodic (e.g. weekly) public reporting of results to allow confident decision making by the U.S. Government (USG), health professionals, and pharmaceutical organizations. ACTIV TRACE is being led by NIH and facilitated by the Foundation for the National Institutes of Health, with participation by the ACTIV public-private partners. For more information about the ACTIV TRACE Initiative and its members, visit


Andrea Sampson, Sampson Public Relations Group

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