Synthetic DNA spike-ins (SDSIs) enable sample tracking and detection of inter-sample contamination in SARS-CoV-2 sequencing workflows

Abstract

The global spread and continued evolution of SARS-CoV-2 has driven an unprecedented surge in viral genomic surveillance. Amplicon-based sequencing methods provide a sensitive, low-cost and rapid approach but suffer a high potential for contamination, which can undermine laboratory processes and results. This challenge will only increase with expanding global production of sequences by diverse laboratories for epidemiological and clinical interpretation, as well in genomic surveillance in future outbreaks. We present SDSI+AmpSeq, an approach which uses synthetic DNA spike-ins (SDSIs) to track samples and detect inter-sample contamination through the sequencing workflow. Applying SDSIs to the ARTIC Consortium’s amplicon design, we demonstrate their utility and efficiency in a real-time investigation of a suspected hospital cluster of SARS-CoV-2 cases and across thousands of diagnostic samples at multiple laboratories. We establish that SDSI+AmpSeq provides increased confidence in genomic data by detecting and in some cases correcting for relatively common, yet previously unobserved modes of error without impacting genome recovery.