Use compount-hets.py to identify samples with compount heterozygous variants. Provide a VCF-like file with phasing information for which parent a variant was inherted from and the script will output files specifying all compound hets found for all samples, and a file for each sample containing only the compound hets for that sample.
To install the software clone the git repository to you local machine or cluster. Once you have cloned the repository it should be ready to use.
git clone https://github.com/gregmcinnes/compound-het-calculator
$ python compound-hets.py --help
usage: compound-hets.py [-h] [-i INPUT] [-p PED] [-t TRANSCRIPT]
[--frequency FREQUENCY] [--consequence CONSEQUENCE]
[-o OUTPUT] [--lookback LOOKBACK] [-d]
This script identifies and reports compound heterozygous variants.
optional arguments:
-h, --help show this help message and exit
-i INPUT, --input INPUT
An input file listing genomic positions and the
patients that have variants at each positions. Each
row represents a single genomic position, with the
chromosome, locus, reference, and alternate alleles
listed (just like a VCF). Also like a VCF, each row
must have an INFO column with information about which
gene the position is in, allele frequency in popular
genomics resources, and predicted allele effect.
-p PED, --ped PED A PED file detailing family and individual
identification numbers, paternal IDs, sex, and
phenotype for each patient. For phenotype
identification, 1 is considered unaffected, 2 is
affected by disease.
-t TRANSCRIPT, --transcript TRANSCRIPT
Optional argument. The name of the gene transcript to
match. Only variants from the specified transcript
will be returned. Only one transcript allowed. If not
specified all transcripts will be considered.
--frequency FREQUENCY
Optional argument. The maximum allele frequency cutoff
allowed. 1000 Genomes, ExAC, and Complete Genomics
allele frequencies are considered. If any of the three
resources reports an allele frequency greater than the
set cutoff the variant will not be considered. If not
specified all variants will all allele frequencies
will be considered.
--consequence CONSEQUENCE
Optional argument. The desired variant consequence
(e.g. missense_variant, nonsense_variant, etc). Only
variants with the specified consequence will be
considered. Multiple consequences may be specified. If
not specified all variants will be considered.
-o OUTPUT, --output OUTPUT
The output directory. The specified output directory
must not already exist. The created directory will
contain all relevant output files.
--lookback LOOKBACK Number of genes to save in local memory. Default=5
-d, --debug Output debugging messages. May be very verbose.
All output files are directed to the directory specified with --output. Two types of files are output as variants are processed: an aggregate file containing all identified compound hets (compound_hets.aggregate.tsv), and family files for each family listing information about each family member and any compound hets they carry (FAMILY_ID.family_file.tsv).