SARS-CoV-2 sequencing with cloud-based analysis illustrates expedient co-ordinated surveillance of viral genomic epidemiology across six continents

BackgroundViral sequencing has made critical contributions to our understanding of and response to the COVID-19 pandemic, but sequencing capacity and bioinformatic expertise remain limited in many settings. This proof-of-principle study aimed to demonstrate the utility of a cloud-based sequencing analysis pipeline, the Tiled Amplicon Pipeline (TAP), for rapid and collaborative SARS-CoV-2 sequencing across seven globally distributed sites. MethodsIn this cross-sectional study from July to August 2022, seven international sites submitted all SARS-CoV-2 sequence data generated over a two-week period to our cloud platform. No patient identifying information was uploaded, and human reads were removed prior to upload to the cloud. Users could opt in to share sample information with collaborators via a tagging system. The pipeline performed sequence assembly, lineage identification and relatedness analysis. ResultsSeven sites contributed 5,432 sequences, of which 5,342 (98.3%) were from clinical samples and 90 (1.7%) were controls. 4,470/5,342 (83.7%) clinical samples had sufficient coverage for lineage assignment. Omicron lineages dominated, with BA.5, BA.4 and BA.2 comprising the vast majority, consistent with contemporary epidemiological observations at the time. Phylogenetic analysis demonstrated low diversity within lineages, and genotypically identical or highly similar sequences were recovered from globally disparate sites. ConclusionsA cloud-based analysis platform like TAP addresses bioinformatic bottlenecks and facilitates international capacity building and collaboration in pathogen surveillance, enhancing global epidemic and pandemic preparedness. ImportanceThe COVID-19 pandemic showed the potential of whole-genome sequencing in informing public health responses, but also highlighted the significant global disparity of sequencing capacity and bioinformatic expertise. In this study, we describe the development and validation of a cloud-based, automated sequencing analysis pipeline for SARS-CoV-2 - the Tiled Amplicon Pipeline (TAP). 5,432 sequences from clinical samples across six continents were collected over a two-week period and processed through TAP, demonstrating its power to co-ordinate secure data sharing and aggregated global analysis. TAP is designed to have the capability to assemble other viruses beyond SARS- CoV-2 that use tiled amplicon sequencing, highlighting its potential to be adapted quickly for use in future outbreaks. Tools such as TAP can simplify access to and interpretation of genomic data, which in turn contributes to a growing global landscape of genomic data sharing and surveillance that underpin pandemic preparedness.