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I’ve recently switched to bwa mem2 and the speed increase is nice for what is basically a drop in replacement (after a bit of validation to make sure that was true). https://github.com/bwa-mem2/bwa-mem2
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Another idea is add in reading cloud data natively e.g. htslib which samtools relies on can read s3 directly. https://github.com/samtools/htslib
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