A Distributed Whole Genome Sequencing Benchmark Study.

Population sequencing often requires collaboration across a distributed network of sequencing centers for the timely processing of thousands of samples. In such massive efforts, it is important that participating scientists can be confident that the accuracy of the sequence data produced is not affected by which center generates the data. A study was conducted across three established sequencing centers, located in Montreal, Toronto, and Vancouver, constituting Canada's Genomics Enterprise (www.cgen.ca). Whole genome sequencing was performed at each center, on three genomic DNA replicates from three well-characterized cell lines. Secondary analysis pipelines employed by each site were applied to sequence data from each of the sites, resulting in three datasets for each of four variables (cell line, replicate, sequencing center, and analysis pipeline), for a total of 81 datasets. These datasets were each assessed according to multiple quality metrics including concordance with benchmark variant truth sets to assess consistent quality across all three conditions for each variable. Three-way concordance analysis of variants across conditions for each variable was performed. Our results showed that the variant concordance between datasets differing only by sequencing center was similar to the concordance for datasets differing only by replicate, using the same analysis pipeline. We also showed that the statistically significant differences between datasets result from the analysis pipeline used, which can be unified and updated as new approaches become available. We conclude that genome sequencing projects can rely on the quality and reproducibility of aggregate data generated across a network of distributed sites.

Informations de copyright

Copyright © 2020 Corbett, Eveleigh, Whitney, Barai, Bourgey, Chuah, Johnson, Moore, Moradin, Mungall, Pereira, Reuter, Thiruvahindrapuram, Wintle, Ragoussis, Strug, Herbrick, Aziz, Jones, Lathrop, Scherer, Staffa and Mungall.

Déclaration de conflit d'intérêts

SS is on the Scientific Advisory Boards of Deep Genomics and Population Bio and intellectual property arising from his research held at The Hospital for Sick Children is licensed by Athena Diagnostics and Lineagen. The Center for Applied Genomics, directed by SS and The Hospital for Sick Children has benefited from joint relationships with Illumina and other suppliers, but none of these arrangements have impacted the studies described in this paper. SS holds the Canadian Institutes of Health Research (CIHR) GlaxoSmithKline Endowed Chair for Genome Sciences at The Hospital for Sick Children and University of Toronto. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.