YoyoMut: Interactive Exploration of SARS-CoV-2 Mutation Fixation and Reversion Through Time.

Reversion of amino acid mutations in structural proteins is common in viral evolution. SARS-CoV-2 provides an unprecedented opportunity for ecological studies, thanks to the abundance of available whole genome sequences. YoyoMut allows regular scanning of open SARS-CoV-2 data, reporting on all cyclic and reverting mutations within all proteins (including Spike), with fine-grained trend visualization distinguishing non-mutated from mutated positions (either fixated or cyclically reversed). In the whole CoVSpectrum database, order of 100 reverting and 50 fixated mutations were identified on Spike. Classification is determined using alternative algorithms (based on threshold or slope inversion); finally, a 3D-protein structure allows us to identify spatial clustering of adjacent mutated positions. Systematic, automated monitoring of these behaviors aids immunologists and structuralists in their manual curation. By generating informative reports, our tool supports daily activities that have practical implications for vaccine and therapeutic anti-Spike monoclonal antibody design: prioritizing analysis of cyclic mutation and reversion models could help avoid the recent failures in their development and inform future strategies.