Phylogeny-aided detection of contamination in nearly 5 million SARS-CoV-2 genomes

Abstract

Contamination can occur during genome sequencing when a contaminant genome is accidentally mixed with the intended genome to be sequenced. Contamination can lead to incorrect consensus genome calling, disrupting analyses of pathogen evolution and transmission. To investigate the extent of this issue, we developed PhyCD, a phylogeny-aided computational approach to investigate contamination in SARS-CoV-2 genome sequencing data. PhyCD masks consensus genome positions associated with suspicious sequencing read coverage drops, then leverages pandemic-scale phylogenetic placement techniques to identify putative contamination events. Applying PhyCD to nearly 5 million SARS-CoV-2 genomes, we identified 10,942 putative contamination events under conservative parameters. Across the flagged genomes, PhyCD flagged -- and so permits masking of -- a total of 64,753 substitutions that could cause errors in downstream genome data analyses.