Robust identification of deletions in exome and genome sequence data based on clustering of Mendelian errors
MEM : Mendelian Error Method to rapidly detect deletions in whole exome and genome trio sequence data
- Variant calling must be performed with one of the following methods
1. Joint calling for the trio
2. Joint genotyping (utilizing gVCFs) followed by VCF merge
- Script provided: ME_UPD_Contamination_Detection_From_TrioVCF.V.0.0.3.pl
- Default Usage: perl ME_UPD_Contamination_Detection_From_TrioVCF.V.0.0.3.pl -i VCF -p pedigreeFile -o output_name
- Additional Arguments:
-i, --input Path to input VCF [required]
-o, --out_prefix Output input name prefix [Default 'output']
-p, --pedigree pedigree file [required]
-V, --VQSRfilter VQSR filter to apply [Default 'yes']
-d, --minDP Minimum read depth required across a Trio [Default 5]
-D, --maxDP Maximum read depth allowed across a Trio [Default 1000]
-c, --minAAD Minimum alternative allele depth [Default 3]
-a, --altBAF Minimum B-allele frequency threshold for homozygous alternate sites i.e. 1/1 [Default 0.9]
-R, --refBAF Maximum B-allele frequency threshold for reference sites i.e. 0/0 [Default 0.1]
-m, --hetBAF_min Minimum B-allele frequency threshold for heterozygous sites i.e. 0/1 [Default 0.2]
-H, --hetBAF_max Maximum B-allele frequency threshold for heterozygous sites i.e. 0/1 [Default 0.8]
-G, --minGQ Minimum genotype quality [Default 30]
-h, --help Usage summary
-v, --verbose Detailed Usage Information
- Read depth, Genotype quality and B-allele frequency filters are built into extraction script
- Other recommended filters:
- Exclude segmental duplication regions
- Exclude common CNV regions
- For WGS data
- Mappability = 1
- Exclude simple repeat regions
- Remove sites that fail Hardy-Weinberg Equilibrium
Note : This step assumes that bedtools V2.26.0 or higher (https://github.com/arq5x/bedtools2) is installed. It can be in the path or full path can be provided using '--tool' argument.
- Script provided: MEM_windowAnalysis.pl
- Default Usage: perl MEM_windowAnalysis.pl -a cases -c caseSample.list_of_files -b backgroundSample.list_of_files -w 2000000 -s 100000
- Additional arguments:
-a, --analysis Analysis type [both or cases]
-b, --bground List of Control Files, ME files must be in bed format [Required if -a is both]
-c, --cases List of Cases Files [Required if run_from is not provided]
-g, --genome Genome file containing start and end of autosomal chromosome in b37 version [Required, provided]
-n, --name Name to attched to intermediate File
-r, --run_from Begin from intermediate steps, available options are Round1, Merge1, Round2, Merge2
-s, --slide Size of slide [Required][Default 100000 ]
-w, --window Size of window [Required][Default 2000000 ]
-t, --tool Full path to bedtools [Required] [Default : bedtools]
-M, --rescue_cases_ME Min ME count to rescue the window in cases after Step1 [Default 5 ]
-X, --filter_bground_ME Max ME count in bground to filter window after Step1 [Default 2 ]
-Y, --filter_cases_ME Min ME count required in cases to consider as a ME cluster [Default 1 ]
-Z, --filter_bground_sample Max Sample count in bground to filter window after Step1 [Default 3 ]
-h, --help Usage summary
-v, --verbose Detailed Usage Information
- We suggest using the first ME and the last ME in the region with the ME cluster as the minimum coordinates for the deletions