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The requirement to uniformly realign and call variants on nearly 5,800 whole genomes (tumour plus normal) presented considerable computational challenges, and raised ethical issues owing to the use of data from different jurisdictions (Extended Data Table 2). To process the data, we adopted a cloud-computing architecture26 in which the alignment and variant calling was spread across 13 data centres on 3 continents, representing a mixture of commercial, infrastructure-as-a-service, academic cloud compute and traditional academic high-performance computer clusters (Supplementary Table 3). Together, the effort used 10 million CPU-core hours.

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