CNVkit coverage takes too long on CRAM file about cnvkit HOT 1 OPEN

Hi @looxon93,

I do not know CRAM a lot, but as far as I can tell samtools handle reference for CRAM through environment variables (see last paragraph)
=> And it may automatically try to download correct reference if not found (not sure about that)
=> So maybe pySAM has a similar behaviour ?
=> That could explain your runtime, it we consider that the whole human genome is downloaded at least once (maybe multiple times ?)

Here is what you can try :

1. Check that FASTA you provided to CNVkit was exacty the same used to generate your CRAM files (looking at contigs, compared to CRAM header etc)
2. Test once again to build a reference from CRAM, but on a few files (like 3)
   => Maybe you could catch this "download genome situation", by looking at this /root/.cache/hts-ref dir during the process ?
3. You may also use samtools to download proper reference and give it as input to CNVkit ?

Hope this helped !
Have a nice day,
Felix

from cnvkit.