Small tutorial of kggseq for mutation burden test of rare mutation samples in a schizophrenia sample

Miaoxin Li (limiaoxin@mail.sysu.edu.cn)

Reference: http://grass.cgs.hku.hk/limx/kggseq/doc10/UserManual.html

Input data:

1. A toy VCF file, examples/simu100.coding.vcf.gz

2. A conventional pedigree file, examples/simu100.ped

3. A text file containing rare mutations sets, examples/ref.mutationrate.txt

4. A text file containing additional covariates of genes, examples/genecov.txt

Purpose: Identify susceptibility genes with rare coding variants for schizophrenia

Run the commands step by step to see what will happen

1. Burden test at genes with rare coding mutations by RUNER

java -Xmx6g -jar kggseq.jar --nt 4 --no-web --vcf-file examples/simu100.coding.vcf.gz --ped-file examples/simu100.ped --out test1 --excel --gty-qual 20.0 --gty-sec-pl 20 --gty-dp 8 --gty-af-ref 0.05 --gty-af-het 0.25 --gty-af-alt 0.75 --ignore-indel --vcf-filter-in PASS --min-obs-rate 0.9 --hwe-all 0.001 --max-allele 3 --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --db-gene refgene,gencode --gene-feature-in 0,1,2,3,4,5,6 --qqplot --gene-freq-score eas --db-score dbnsfp --disease-causing-predict best --runer-gene-coding

2. Burden test by RUNER with a reference

3. Burden test by RUNER with additional covariates of genes

4. Burden test by RUNER using local control samples

java -Xmx6g -jar kggseq.jar --nt 4 --no-web --vcf-file examples/simu100.coding.vcf.gz --ped-file examples/simu100.ped --out test1 --excel --gty-qual 20.0 --gty-sec-pl 20 --gty-dp 8 --gty-af-ref 0.05 --gty-af-het 0.25 --gty-af-alt 0.75 --ignore-indel --vcf-filter-in PASS --min-obs-rate 0.9 --hwe-all 0.001 --max-allele 3 --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --db-gene refgene,gencode --gene-feature-in 0,1,2,3,4,5,6 --qqplot --gene-freq-score CONTROL --db-score dbnsfp --disease-causing-predict best --runer-gene-coding

5. Burden test by RUNER at other types of coding variants

java -Xmx6g -jar kggseq.jar --nt 4 --no-web --vcf-file examples/simu100.coding.vcf.gz --ped-file examples/simu100.ped --out test1 --excel --gty-qual 20.0 --gty-sec-pl 20 --gty-dp 8 --gty-af-ref 0.05 --gty-af-het 0.25 --gty-af-alt 0.75 --ignore-indel --vcf-filter-in PASS --min-obs-rate 0.9 --hwe-all 0.001 --max-allele 3 --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --db-gene refgene,gencode --gene-feature-in 0,1,2,3,4,5,6 --qqplot --gene-freq-score eas --response-gene-feature 2,3,4,5,6 --db-score dbnsfp --disease-causing-predict best --runer-gene-coding

6. Burden test at genes with rare coding mutations by unweighted RUNER

7. Burden test by RUNER and search related papers in PubMed