Rapid detection of inter-clade recombination in SARS-CoV-2 with Bolotie.

The ability to detect recombination in pathogen genomes is crucial to the accuracy of phylogenetic analysis and consequently to forecasting the spread of infectious diseases and to developing therapeutics and public health policies. However, in case of the SARS-CoV-2, the low divergence of near-identical genomes sequenced over a short period of time makes conventional analysis infeasible. Using a novel method, we identified 225 anomalous SARS-CoV-2 genomes of likely recombinant origins out of the first 87,695 genomes to be released, several of which have persisted in the population. Bolotie is specifically designed to perform a rapid search for inter-clade recombination events over extremely large datasets, facilitating analysis of novel isolates in seconds. In cases where raw sequencing data was available, we were able to rule out the possibility that these samples represented co-infections by analyzing the underlying sequence reads. The Bolotie software and other data from our study are available at https://github.com/salzberg-lab/bolotie.