Electrical Engineering and Computer Science Faculty Publications

Document Type

Article

Publication Title

PLoS Computational Biology

Abstract

We have developed a robust method for efficiently tracking multiple co-occurring mutations in a sequence database. Evolution often hinges on the interaction of several mutations to produce significant phenotypic changes that lead to the proliferation of a variant. However, identifying numerous simultaneous mutations across a vast database of sequences poses a significant computational challenge. Our approach leverages a matrix factorization technique to automatically and efficiently pinpoint subsets of positions where co-mutations occur, appearing in a substantial number of sequences within the database. We validated our method using SARS-CoV-2 receptor-binding domains, comprising approximately seven hundred thousand sequences of the Spike protein, demonstrating superior performance compared to a reasonably exhaustive brute-force method. Furthermore, we explore the biological significance of the identified co-mutational positions (CMPs) and their potential impact on the virus’s evolution and functionality, identifying key mutations in Delta and Omicron variants. This analysis underscores the significant role of identified CMPs in understanding the evolutionary trajectory. By tracking the “birth” and “death” of CMPs, we can elucidate the persistence and impact of specific groups of mutations across different viral strains, providing valuable insights into the virus’ adaptability and thus, possibly aiding vaccine design strategies. © 2025 Kolar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI

10.1371/journal.pcbi.1012391

Publication Date

2025

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