Question

Running Sift And Polyphen In Mouse And Other Species

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11.0 years ago

jeansimon32 ▴ 170

Hello,

Can we annotate missense mutations in other species (e.g. mouse) with Sift and Polyphen? If not, what are the equivalent software for mouse?

Thanks
Simon

sift polyphen • 7.7k views

ADD COMMENT • link updated 2.1 years ago by Ram 44k • written 11.0 years ago by jeansimon32 ▴ 170

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To run Polyphen2 on mouse genes you will have to build the mouse database from scratch. The steps required can be read in the Polyphen2 manual. Download the Polyphen2 binaries and build your mouse database using protein sequences from UniProt. You can then use command line to find out how deleterious is the missense mutation.

ADD REPLY • link 11.0 years ago by Ashutosh Pandey 12k

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Hi, I saw your post and thought to ask for help.

I am trying to build the mouse database from scratch to use polyphen2 using the manual, but I keep getting the following error:

/Software/polyphen-2.2.2/bin/run_pph.pl mouse.test.input 1>mouse.test.output
DBD::SQLite::db prepare failed: no such table: id2acc at /NGS/Software/polyphen-2.2.2/perl/PPH/Seq.pm line 89, <> line 1.

Not sure why and what is going wrong. Any help will be much appreciated.

Thanks,
Saumya

ADD REPLY • link updated 2.1 years ago by Ram 44k • written 9.3 years ago by somseeprags • 0

score 2 · Answer 1 · 2013-11-08

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11.0 years ago

Emily 24k

You can absolutely run SIFT on any species. In Ensembl, we have SIFT predictions for every possible amino acid change in the genome for human, mouse, rat, dog, chicken and cow, and will be introducing sheep in our next release in December. We also have PolyPhen predictions for human.

ADD COMMENT • link 11.0 years ago by Emily 24k

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Hi Emily,

I had a follow-up question for you about running SIFT in the dog. I see here that it should be possible, and I see that SIFT is available on Ensembl's web page for the dog. I'm running VEP locally on our cluster as recommended, but when I add the --sift flag to my command prompt, I get an error message that SIFT doesn't exist for this species. Is there a separate database I need to download? I also tried running VEP without the --cache option to force the command line to use Ensembl's server, but I still got the same error message.

Any suggestions on how to get this running from the command line?

Thanks!

ADD REPLY • link 10.3 years ago by steven_friedenberg ▴ 10

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Please do not cross-post to BioStar and Ensembl helpdesk.

ADD REPLY • link 10.3 years ago by Emily 24k

score 1 · Answer 2 · 2013-11-08

For SIFT, I believe the tools they list at the bottom of their Page you may be able to do non-human proteins. Especially if you pre-construct a multiple sequence alignment for a specific protein of interest. PolyPhen2 I think does have experimental support for non-human organisms, but I think only in the stand-along version you can download, not on their web interface. PROVEAN, also from JCVI like SIFT, can do predictions for any organism.