Step 4 eDiVA-Prioritize

This is the final step of the pipeline where variants are filtered and selected, depending on the pedigree information, the disease inheritance profile, and the strictness of the filter:

Command example

nextflow run eDiVA-prioritize.nf --OUTF ./\
        --ANNOTATED combined.variants.supplement.ranked.csv \ 
        --MODE standard \
        --PEDIGREE pedigree.tree \
        --FAMILY_TYPE trio \
        --HPO hpo_list.txt \
        --EXCLUSIONLIST edivapath/Resource/gene_exclusion_list.txt \
        --INHERITANCE choose

Params

• ANNOTATED: The ranked.csv file output from eDiVA-Annotate.nf
• OUTF : Output folder
• MODE : standard or strict
• PEDIGREE : pedigree.tree file output from Step 1.5
• FAMILY_TYPE : trio (for parent-child trios) or family (other analyses)
• HPO_list= Text file with HPO terms to be used for soft filtering. It can point to an empty file such as in Resource/empty_list.txt'* .
• EXCLUSIONLIST : Genes excluded because normally are false postitives . A default list is present in '//Resource/gene_exclusion_list.txt but it can point to an empty file
• INHERITANCE : Inheritance mode for the disease to chose among
  • 'dominant_inherited'
  • 'recessive'
  • 'dominant_denovo'
  • 'Xlinked'
  • 'compound'

Output

• Folder with the inheritance type e.g dominant_denovo
  • combined.variants.supplement.dominant_inherited.csv : All variants annotated with an extra column explaining if they are compatible with the inheritance pattern provided
  • combined.variants.supplement.filtered.dominant_inherited.csv : Only the variants passing the filters are reported here, sorted by eDiVA-Score
  • combined.variants.supplement.filtered.dominant_inherited.csv.xlsx : Excel file with the selected variants, with extra OMIM and Clinvar information where available
• variant_prioritization_report.xlsx
  • This file is updated with the current information. It is an excel file with one spreadsheet for each inheritance type. In this way you can have all analyses results in one file only

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#Docker execution

Provided you have edited the nextflow.config file accordingly to docker usage and you produced the correct family_config file with container paths, the execution is the following:

nextflow run eDiVA-prioritize.nf --OUTF ./\
        --ANNOTATED combined.variants.supplement.ranked.csv \ 
        --MODE standard \
        --PEDIGREE pedigree.tree \
        --FAMILY_TYPE trio \
        --HPO hpo_list.txt \
        --EXCLUSIONLIST edivapath/Resource/gene_exclusion_list.txt \
        --INHERITANCE choose \
        -with docker ediva:code