Genome Alert! framework
Genome Alert! is an automatic monitoring and curating method of variant pathogenicity and genotype-phenotype knowledge in ClinVar database.
Genome Alert! is build in 3 parts :
- ClinVCF monitors submissions and extracts clinical information from a Clinvar XML monthly Full Release into an easy-to-manipulate standard VCF 4.2 file.
In order to reclassify high confidence pathogenic variants with a conflicting interpretation of pathogenicity status, ClinVCF first removes ACMG classification outliers submissions for variants with at least 4 submissions according to the 1.5 * Interquartile Range method. Secondly, it reclassifies the variant status according to the ClinVar classification system and finally we set the reclassification confidence with a three-tier level system. https://github.com/SeqOne/clinvcf
- Variant Alert! track every significant changes in variant classification and gene-disease association between two versions of ClinVCF VCFs, including their “breaking change” status defined according to the suspected clinical impact of these changes. A major change is defined as a potential direct impact on clinical diagnosis. A minor change is a change in confidence classification (e.g. Pathogenic to Likely Pathogenic status). https://github.com/SeqOne/variant_alert
- ClinVarome gathers and processes all ClinVar knowledge available through time. Through an unsupervised clustering model, it classifies clinical validity of information for each gene with a four-clusters system https://github.com/SeqOne/clinvarome.
You can implement this framework with these three open source repositories.
If you prefer, this shiny app provides monthly updated results of Genome Alert!.
You can download this results as a TSV file and explore the data through the app.
The code and description to process data and display the App is available here : https://github.com/SeqOne/GenomeAlert_app.
How to cite
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).
Genome Alert! is a collaboration of the Université Grenoble Alpes, SeqOne and CHU de Rouen.
Legal notice (under French law) are available here.