Topology identifies emerging adaptive mutations in SARS-CoV-2

The COVID-19 pandemic has lead to a worldwide effort to characterize its evolution through the mapping of mutations in the genome of the coronavirus SARS-CoV-2. As the virus spreads and evolves it acquires new mutations that could have important public health consequences, including higher transmissibility, morbidity, mortality, and immune evasion, among others. Ideally, we would like to quickly identify new mutations that could confer adaptive advantages to the evolving virus by leveraging the large number of SARS-CoV-2 genomes. One way of identifying adaptive mutations is by looking at convergent mutations, mutations in the same genomic position that occur independently. The large number of currently available genomes, more than a million at this moment, however precludes the efficient use of phylogeny-based techniques. Here, we establish a fast and scalable Topological Data Analysis approach for the early warning and surveillance of emerging adaptive mutations of the coronavirus SARS-CoV-2 in the ongoing COVID-19 pandemic. Our method relies on a novel topological tool for the analysis of viral genome datasets based on persistent homology. It systematically identifies convergent events in viral evolution merely by their topological footprint and thus overcomes limitations of current phylogenetic inference techniques. This allows for an unbiased and rapid analysis of large viral datasets. We introduce a new topological measure for convergent evolution and apply it to the complete GISAID dataset as of February 2021, comprising 303,651 high-quality SARS-CoV-2 isolates taken from patients all over the world since the beginning of the pandemic. A complete list of mutations showing topological signals of convergence is compiled. We find that topologically salient mutations on the receptor-binding domain appear in several variants of concern and are linked with an increase in infectivity and immune escape. Moreover, for many adaptive mutations the topological signal precedes an increase in prevalence. We demonstrate the capability of our method to effectively identify emerging adaptive mutations at an early stage. By localizing topological signals in the dataset, we are able to extract geo-temporal information about the early occurrence of emerging adaptive mutations. The identification of these mutations can help to develop an alert system to monitor mutations of concern and guide experimentalists to focus the study of specific circulating variants.