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Diagnostic Analysis Workflow

This diagnostic analysis workflow has been developed to filter for and prioritize pathogenic variation/mutation in patient samples.

Relevant reading material:
  • Petrovski, Slavé, et al. "Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study." The Lancet (2019).
  • Zhu X, et al. "Whole exome sequencing in undiagnosed genetic diseases: Interpreting 119 trios." Genetics in Medicine (2015).

Variant filtration:

ATAV Commands:

Trio (or Duo) analysis

Rare variants:

atav.sh --list-trio --impact HIGH,MODERATE,LOW --min-ad-alt 3 --qual 30 --gq 20 --filter pass,likely,intermediate --max-default-control-af 0.01 --max-gnomad-exome-af 0.01 --max-gnomad-genome-af 0.01 --include-qc-missing --sample $SAMPLE --out $OUTPUT

Modifier known variants:

atav.sh --list-trio --known-var-pathogenic-only --modifier-only --min-ad-alt 3 --qual 30 --gq 20 --filter pass,likely,intermediate --include-qc-missing --sample $SAMPLE --out $OUTPUT

Singleton analysis

Rare variants:

atav.sh --list-singleton --impact HIGH,MODERATE,LOW --min-ad-alt 3 --qual 30 --gq 20 --filter pass,likely,intermediate --max-default-control-af 0.01 --max-gnomad-exome-af 0.01 --max-gnomad-genome-af 0.01 --include-qc-missing --sample $SAMPLE --out $OUTPUT

Modifier known variants:

atav.sh --list-singleton --known-var-pathogenic-only --modifier-only --min-ad-alt 3 --qual 30 --gq 20 --filter pass,likely,intermediate --include-qc-missing --sample $SAMPLE --out $OUTPUT

Coverage Summary (for trio & singleton): 

atav.sh --coverage-summary --gene-boundaries /nfs/goldstein/software/atav_home/data/ccds/addjusted.CCDS.genes.index.r20.hg19.txt --min-coverage 10 --percent-region-covered .9 --sample $SAMPLE --out $OUTPUT

Note: all the external dataset are used in variant prioritization / tier classification will be included by default.

Example output

/nfs/goldstein/software/atav_home/example/diagnostic

Variant prioritization:

Variant reviewing SOP (adding soon)