Small tutorial of kggseq for annotation and association of sequence variants at a  schizophrenia  sample

Miaoxin Li (limx54@163.com)

 

Reference: https://pmglab.top/kggseq/doc10/UserManual.html

 

Input data:

1.      A toy VCF file,  examples/assoc.hg19.vcf.gz

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

3.     A text file containing functional sets of genes, examples/geneset.txt

Purpose: Identify potential pathogenic rare variants, genes and pathways for schizophrenia   


Run the commands step by step to see what will happen

1.      Annotate sequence variants by RefGenes, and GEncode models:

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel  

2.      Pathogenic predictions at non-synonymous and non-coding variants

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel  --db-score dbnsfp,dbncfp_known --mendel-causing-predict best --regulatory-causing-predict all --filter-nondisease-variant

 

3.      Association at rare and low-frequency variants

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel --db-score dbnsfp,dbncfp_known --mendel-causing-predict best --regulatory-causing-predict all --filter-nondisease-variant --var-assoc --qqplot

4.      Association at rare and low-frequency variants by RVTest

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel --db-score dbnsfp,dbncfp_known --mendel-causing-predict best --regulatory-causing-predict all --filter-nondisease-variant --qqplot --rvtest-var --rvtest-vcf --phe disease1 --cov sex,age

5.      Association at rare variants of genes by SKAT

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel --db-score dbnsfp,dbncfp_known --mendel-causing-predict best --regulatory-causing-predict all --filter-nondisease-variant --db-filter 1kg201305 --rare-allele-freq 0.01 --qqplot --skat-gene  --skat-cutoff 5 --phe disease1 --cov sex,age

6.      Association at rare variants of genes by RVTest and search related papers in PubMed

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel --db-score dbnsfp,dbncfp_known --mendel-causing-predict best --regulatory-causing-predict all --filter-nondisease-variant --db-filter 1kg201305 --rare-allele-freq 0.01 --qqplot --rvtest-gene --rvtest-vcf --phe disease1 --cov sex,age --phenotype-term schizophrenia --pubmed-mining-top-gene 10

7.      Prioritize sequence variants by OMIM information, phenolyzer and mouse phenotypes

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel --db-score dbnsfp,dbncfp_known --mendel-causing-predict best --regulatory-causing-predict all --filter-nondisease-variant --db-filter 1kg201305 --rare-allele-freq 0.01 --qqplot --rvtest-gene --phe disease1 --cov sex,age --geneset-db cura --omim-annot --mouse-pheno --phenolyzer-prediction --phenotype-term schizophrenia

8.      Association at rare variants of genesets by SKAT

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel --db-score dbnsfp,dbncfp_known --mendel-causing-predict best --regulatory-causing-predict all --filter-nondisease-variant --db-filter 1kg201305 --rare-allele-freq 0.01 --qqplot --skat-geneset --phe disease1 --cov sex,age --geneset-file examples/geneset.txt

9.      Association at rare variants of genesets by RVTest

java -Xmx6g -jar kggseq.jar --nt 4 --vcf-file examples/assoc.hg19.vcf.gz --ped-file examples/assoc.ped --out test1 --excel --db-score dbnsfp,dbncfp_known --mendel-causing-predict best --regulatory-causing-predict all --filter-nondisease-variant --db-filter 1kg201305 --rare-allele-freq 0.01 --qqplot --rvtest-geneset --rvtest-vcf --phe disease1 --cov sex,age --geneset-file examples/geneset.txt