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

Miaoxin Li ( limx54@163.com)

Reference: https://pmglab.top/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 RUNNER

java -Xmx6g -jar kggseq.jar --nt 4 --no-web --vcf-file examples/simu100.coding.vcf.gz --ped-file examples/simu100.ped --out test1 --excel   --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --min-case-control-freq-ratio 3 --qqplot --gene-freq-score eas --db-score dbnsfp --disease-causing-predict best --RUNNER-gene-coding



2. Burden test by RUNNER with a reference  

java -Xmx6g -jar kggseq.jar --nt 4 --no-web --vcf-file examples/simu100.coding.vcf.gz --ped-file examples/simu100.ped --out test1 --excel   --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --min-case-control-freq-ratio 3  --qqplot --gene-freq-score eas --db-score dbnsfp --disease-causing-predict best --runner-gene-coding --ref-mut-sample examples/ref.mutationrate.txt

3. Burden test by RUNNER with additional covariates of genes

java -Xmx6g -jar kggseq.jar --nt 4 --no-web --vcf-file examples/simu100.coding.vcf.gz --ped-file examples/simu100.ped --out test1 --excel   --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --min-case-control-freq-ratio 3  --qqplot --gene-freq-score eas --db-score dbnsfp --disease-causing-predict best --runner-gene-coding --gene-cov-file examples/genecov.txt

4. Burden test by RUNNER 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   --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --min-case-control-freq-ratio 3  --qqplot --gene-freq-score CONTROL --db-score dbnsfp --disease-causing-predict best --runner-gene-coding

5. Burden test by RUNNER 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   --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --min-case-control-freq-ratio 3  --qqplot --gene-freq-score eas --response-gene-feature 2,3,4,5,6  --db-score dbnsfp --disease-causing-predict best --runner-gene-coding

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

java -Xmx6g -jar kggseq.jar --nt 4 --no-web --vcf-file examples/simu100.coding.vcf.gz --ped-file examples/simu100.ped --out test1 --excel   --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --min-case-control-freq-ratio 3  --qqplot --gene-freq-score eas --db-score dbnsfp --disease-causing-predict best --uwrunner-gene-coding

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

java -Xmx6g -jar kggseq.jar --nt 4 --no-web --vcf-file examples/simu100.coding.vcf.gz --ped-file examples/simu100.ped --out test1 --excel   --db-filter gadexome.eas,gadgenome.eas,1kgeas201305 --rare-allele-freq 0.01 --min-case-control-freq-ratio 3  --qqplot --gene-freq-score eas --db-score dbnsfp --disease-causing-predict best --runner-gene-coding --phenotype-term schizophrenia --pubmed-mining-top-gene 10