Author: Berke Cagkan Toptas
Many tools exists to count Mendelian violations in family trios using the naive variant comparison method where variants at same locations are compared. Naive variant comparison however, fails to assess regions where multiple variants need to be examined together. This reduces the accuracy of existing Mendelian violation checking tools.
Variants can be represent with different ways due to the current VCF file standard and repetitive structure of human genome. In Figure A, an example is provided where a small INDEL can be represented as 3 variants. This representation issues often cause wrong Mendelian decision assessment in naive variant comparison. In Figure B, an example is given where naive tools marks all 4 variants as Mendelian violation. However, when we apply them to the reference sequence, a possible combination can be found where none of them are Mendelian violation.
With VBT, we aim to resolve variant representation issues in family trios and perform more accurate trio analysis for several purposes including benchmarking and de novo mutation identification. VBT uses an improved version of vcfeval and uses htslib to read/write VCF and FASTA files.
./vbt mendelian -father <father_vcf_path> -mother <mother_vcf_path> -child <child_vcf_path> -ref <reference_fasta> -outDir <output_directory> [OPTIONAL PARAMETERS]
Warning: Parameters are case sensitive!
A single parameter which prints all parameter options to the console. (./vbt mendelian --help)
A required parameter which specifies the father vcf file path. It supports both vcf.gz and vcf file formats. If given vcf contain multiple samples, first sample will be taken by default unless a Pedigree file is provided (see -pedigree command)
A required parameter which specifies the mother vcf file path. It supports both vcf.gz and vcf file formats. If given vcf contain multiple samples, first sample will be taken by default unless a Pedigree file is provided (see -pedigree command)
A required parameter which specifies the mother vcf file path. It supports both vcf.gz and vcf file formats. If given vcf contain multiple samples, first sample will be taken by default unless a Pedigree file is provided (see -pedigree command)
A required parameter which specifies the reference FASTA file path. It should be in FASTA (.fa) format. A FASTA index file is not mandatory. The tool will automatically generate a FASTA index file (.fai) if it does not exist.
An optional parameter which sets the way program process no call variants. Default mode is explicit.
explicit : Marks noCall(variants with ./. genotype) variants as NoCall (Parent nocall or child nocall)
none : Process noCall sites as 0/0 HOMREF
A required parameter which specifies the output directory for program/error logs and ga4gh output vcf file. In current version, in order not to damage multiplatform capability, directory should exist. VBT will not generate a directory to be able to support different Operating Systems.
An optional parameter which specifies the prefixes of generatet output file names. Default prefix is 'out'.
An optional output mode intended as an intermediate result for de Novo mutation callers. Outputs all violation regions as a BED file for further processing.
An optional parameter which is used to determine all 3 samples from a PED file. Is useful where input vcf files contain more than 1 sample
An optional parameter which is used to process only autosomes [chr1:chr22] By default, it is set to FALSE. Note that in order to use this parameter, the chromosome naming should be either 1,2,3 etc. or chr1, chr2, chr3. For other chromosome namings, please use -bed command to specify autosomes.
An optional parameter which is used to select regions from VCF file.
An optional parameter which is used to filter variants with given filter name. Filter name should be same in baseline and called variants. By default, PASS filtering is applied to the variants. In order to disable filtering, '-filter none' should be used.
An optional parameter which is used to disable reference overlapping mode in variant comparison operation. Variants that are overlapping will be count as violation without any trimming process.
An optional parameter which is used to output selected INFO columns in generated output trio VCF. Tags should be given as comma separated without whitespace. Each tag is should be exist in all mother, father and child samples. Info tag selection order is child, father and mother respectively.
An optional parameter which is used to specify number of threads that will be used for variant comparison step of trio analysis. Default value is 2.