Question: Does truvari have a upper limit on the file size? How to speed up? about truvari HOT 2 CLOSED

Using -f (--reference) is the problem here because it needs to fetch reference sequence for every variant. The --reference parameter has been kept for backwards compatibility, but is no longer recommended. The default 'unroll' sequence comparison technique (details) is faster and also more accurate (see supplementary figure 7).

Try without -f and --minhaplen and it should run similarly to --pctseq 0

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Also, I see that you're using --keep common which requires checking variants' genotypes. pysam is pretty slow at accessing genotypes. I just committed a change to develop that reduces how often they need to be accessed. I'm working on a ~50 sample VCF right now and this change is ~2x-5x faster with identical results. So if you'd like to install from develop of the repo, that should help, too. There's also a change to how --gt is used which helps, but since you're not using that parameter, you won't see the speedup.

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