ClinVarome is a list of genes involved in human disease, based on ClinVar database extraction via Genome Alert!.
ClinVarome annotation allows enhanced ClinVarome with useful annotations for genetic diagnostics.
It provides for each gene:
- Clinical features extracted from clinVCF VCF file
- Molecular consequences reported
- Date of first and last apparition of pathogenic variant
- Number of reported (likely) pathogenic variants
Based on the following features, the annotation provides also a clinical validity score for genes generated by a Agglomerative Clustering model :
- Date between first and last apparition of pathogenic variant
- Number of reported (likely) pathogenic variants
- Highest review confidence variant status in (likely) pathogenic variant
- Highest ACMG classification variant status
ClinVarome annotation is developped in python > 3.6, and need Genome Alert! processed data.
ClinVarome tool is a part of the Genome Alert! framework - Website https://genomealert.univ-grenoble-alpes.fr/.
ClinVarome annotation need for a ClinVar release :
- a VCF file from ClinVCF
- a ClinVarome file from Variant Alert!
- a concatenated file of all Variant Alert! compare-variant output (compare-variant_total.tsv.gz)
- a concatenated file of all Variant Alert! compare-gene output (compare-gene_total.tsv.gz)
Run ClinVarome
poetry install
#For testing
mkdir OUTPUT_DIR
poetry run clinvarome/clinvarome_annotation.py \
--vcf tests/full_data/clinvar_GRCh38_{latest}.vcf.gz \
--clinvarome tests/full_data/clinvarome_{latest}.tsv \
--compare-gene tests/full_data/compare-gene_total.tsv.gz \
--compare-variant tests/full_data/compare-variant_total.tsv.gz \
--output-dir OUTPUT_DIR/usage: clinvarome_annotation.py [-h] --vcf VCF_FILE --clinvarome CLINVAROME
--compare-gene COMPARE_GENE --compare-variant
COMPARE_VARIANT [--max-date MAX_DATE]
[--gnomad] [--manual-score] --output-dir
OUTPUT_DIR
Add additional annotations to the ClinVarome.
optional arguments:
-h, --help show this help message and exit
--vcf VCF_FILE vcf input from clinVCF
--clinvarome CLINVAROME
ClinVarome file from Variant Alert! to be annotated.
--compare-gene COMPARE_GENE
Variant Alert! compare gene concatenation file of all
previous ClinVar release.
--compare-variant COMPARE_VARIANT
Variant Alert! compare variant concatenation file of
all previous ClinVar release.
--gnomad Add max pathogenic gnomAD filtered allele frequency
for each gene, if clinVCF is annotated with gnomAD v3
by vcfanno.
--output-dir OUTPUT_DIR
Path to the output folder.ClinVarome annotation generate an enhanced ClinVarome TSV (file with additional suffix _clinvarome_annotation.tsv).
If you use a tool of the Genome Alert! framework, please cite:
Yauy et al., Genome Alert!: a standardized procedure for genomic variant reinterpretation and automated genotype-phenotype reassessment in clinical routine. medRxiv (2021). https://doi.org/10.1101/2021.07.13.21260422
ClinVarome is licensed under the Apache License, Version 2.0. See LICENSE for the full license text.
ClinVarome is a part of the Genome Alert! framework, a collaboration of :
