Are there any tools to identify compound heterozygous variants in resequencing data? By compound heterozygosity I mean a catalog of multiple deleterious mutations (PolyPhen? or SIFT?) that happen to fall as hets into different locations of the same genes.
My lab is working on a project called gemini for exploring genomic variation in the context of genome annotations. Briefly, you load a VCF (eventually BCF2) into our local sqlite database framework and from there you can explore the variation therein in several ways. Take a look through the README for details. The project is still in an alpha state, but we do have a tool for detecting compound heterozygotes from VCF files that have phased genotypes. This section of the README covers it, but the workflow would be as follows:
# load a VCF that has been annotated by snpEff
> gemini load -v my.vcf -t snpEff my.vcf.db
# extract candidate compound hets
> gemini comp_hets my.vcf.db
sample gene het1 het2
NA19002 GTSE1 chr22,46722400,46722401,G,A,G|A,stop_gain,exon_22,0.005,1 chr22,46704499,46704500,C,A,A|C,stop_gain,exon_22,0.005,0
# restrict to compound hets that are clearly loss-of-function
> gemini comp_hets --only_lof my.vcf.db
Hi Aaronquinlan,
I am trying to use gemini comp_hets tool to filter for compound heterozygous mutations from whole exome sequencing data. It worked perfectly on one of my datasets, but it seemed to be failed on the other. So I am wandering is there any prerequisite for the VCF file, such as any specific TAG in FORMAT field is required for your phasing step? And I am guessing the problem may due to the absence of phased genotype in that VCF file. Could you indicate the specific amount of phased genotypes in the VCF in order to have the comp_hets tool work?
More specifically, I was able to load VCF (after normalization and snpeff) and PED files. The comp_hets tool does not produce any error but just being running for more than 20h hours and the size of the output file stayed at 0. Could that be the VCF is too large (there are more than 240 samples in the VCF)? But the thing is the output file does not grow. I also tried to limit the analysis to a single family, then the program was able to finish but still gives an empty output.
Could you please help figure out any possible reasons for my situation? Many thanks!!
Hello,
I have written a software called genmod to annotate the common genetic models in VCF files, including compound heterozygotes.
It works with arbitrary pedigrees, including single individuals and can also take phasing into account.
Hope this can help out!
When I am trying via PIP then getting this errors.
creating build/temp.linux-x86_64-2.7
creating build/temp.linux-x86_64-2.7/pysam
creating build/temp.linux-x86_64-2.7/samtools
creating build/temp.linux-x86_64-2.7/samtools/misc
creating build/temp.linux-x86_64-2.7/samtools/bcftools
x86_64-linux-gnu-gcc -pthread -fno-strict-aliasing -DNDEBUG -g -fwrapv -O2 -Wall -Wstrict-prototypes -fPIC -D_FILE_OFFSET_BITS=64 -D_USE_KNETFILE= -Isamtools -Ipysam -I/usr/include/python2.7 -c pysam/csamtools.c -o build/temp.linux-x86_64-2.7/pysam/csamtools.o -Wno-error=declaration-after-statement
pysam/csamtools.c:8:22: fatal error: pyconfig.h: No such file or directory
#include "pyconfig.h"
^
compilation terminated.
error: command 'x86_64-linux-gnu-gcc' failed with exit status
and getting this error while using git too
git clone git@github.com:moonso/genmod.git
Cloning into 'genmod'...
Warning: Permanently added the RSA host key for IP address '192.30.252.128' to the list of known hosts.
Permission denied (publickey).
fatal: Could not read from remote repository.
Please make sure you have the correct access rights
and the repository exists.
The VAAST paper described how you can identify compound heterozygous mutations. It can also handle locus heterogeneity. Sorry for the loose language.
...just to enrich the survey/discussion...I recently faced the same task,
and found also this paper: Filtering for Compound Heterozygous Sequence Variants in Non-Consanguineous Pedigrees
Their tool is online here
Just like "yet another short-read mapper" I think we need a "yet another web-only tool" category. Don't get me wrong, I think making web tools is great in order to have good tools used by more than just bioinformaticians, but writing web-only services is getting tiring. Many of us, for legal reasons, should not be uploading our samples to outside servers.
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version 2.3.6
To call a 'compound heterozygous' I think you need the parents otherwise it might be just double hets. What are the files you have: BAM , VCF, etc?