Genome Alert! framework

Genome Alert! is an automatic monitoring and curating method of variant pathogenicity and genotype-phenotype knowledge in ClinVar database.

Genome Alert! logo

The Framework

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.

The webapp

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).

Credits

Genome Alert! is a collaboration of the Université Grenoble Alpes, SeqOne and CHU de Rouen.

Legal notice (under French law) are available here.

ClinVar mendelian genome

Download ClinVarome list

Compare genes

to
Download Gene Alert list

Compare variants

to
Download Variant Alert list