What is it about?

The overall idea is that large numbers of genomes, 50,000 when we did the study, contain non-trivial information that can be retrieved by a global method. The global method means that all the variations in all the genomes at once are fit to one and the same model. According to classical results due to Motoo Kimura from the 1960s, these pairwise terms are directly related to pairwise fitness. They hence point to combinatorial dependencies and potential combinatorial weaknesses in e.g. pathogens such as SARS-CoV-2. Our work also highlights the pioneering contribution of Kimura to the population biology of highly recombinant organisms.

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Why is it important?

The global pandemic of COVID19 is a worldwide threat to human health and the world economy. Any new tool that can help fight the pandemic is potentially important, even if still in the form of basic research. Our work also demonstrates that more information than usually done can be obtained from all the SARS-CoV-2 genomes collected and deposited in standard repositories such as GISAID.


First, it was quite satisfying to be able to use methods developed by my group and the community over several years on an issue of high societal importance. We hope that in follow-up studies we and/or others will be able to do more. For instance, the number of SARS-CoV-2 genomes on GISAID is continuously increasing, and it would be interesting to track the predictions we made over time. It would also be interesting to find ways to leverage all the meta-data contained in GISAID, such as which lab contributed the data (proxy for geographic location), exact date of sampling, etc. Finally, we hope that the results obtained in the paper, or that will be obtained in follow-up studies, will yield tools to help fight COVID19 disease.

Erik Aurell
Kungliga Tekniska Hogskolan

The predicted pairwise epistasis could be served as the null hypothesis for the design of biological experiments. These significant links could be helpful also for the development of combinatorial treatment of COVID19.

Hongli ZENG
Nanjing University of Posts and Telecommunications

Read the Original

This page is a summary of: Global analysis of more than 50,000 SARS-CoV-2 genomes reveals epistasis between eight viral genes, Proceedings of the National Academy of Sciences, November 2020, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2012331117.
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