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Updated: Oct 15, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Data-driven analysis of amino acid change dynamics timely reveals SARS-CoV-2 variant emergence
Anna Bernasconi1, Lorenzo Mari2, Renato Casagrandi2
1Departement of Electronics, Information, and Bioengineering, Politecnico di Milano, 20133, Milan, Italy. anna.bernasconi@polimi.it.
Abstract:
Since its emergence in late 2019, the diffusion of SARS-CoV-2 is associated with the evolution of its viral genome. The co-occurrence of specific amino acid changes, collectively named 'virus variant', requires scrutiny (as variants may hugely impact the agent's transmission, pathogenesis, or antigenicity); variant evolution is studied using phylogenetics. Yet, never has this problem been tackled by digging into data with ad hoc analysis techniques. Here we show that the emergence of variants can in fact be traced through data-driven methods, further capitalizing on the value of large collections of SARS-CoV-2 sequences. For all countries with sufficient data, we compute weekly counts of amino acid changes, unveil time-varying clusters of changes with similar-rapidly growing-dynamics, and then follow their evolution. Our method succeeds in timely associating clusters to variants of interest/concern, provided their change composition is well characterized. This allows us to detect variants' emergence, rise, peak, and eventual decline under competitive pressure of another variant. Our early warning system, exclusively relying on deposited sequences, shows the power of big data in this context, and concurs to calling for the wide spreading of public SARS-CoV-2 genome sequencing for improved surveillance and control of the COVID-19 pandemic.
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