Query Samples

Queries allow the filtering of sample variants, to investigate relations to other samples, to load virtual gene panels (gene names or genomic relevant regions) and predefined standardised filters.

Sample selection

A sample identifier is searched and selected across all accessible VCF files. The list can be filtered by the sample and file name. To select a sample, double-click on its name.

Virtual Gene Panel

Disease specific panels can be pre-defined in DART to simplify analyses of known phenotypes. Panels can be defined as HGNC gene names or as genomic relevant regions in BED file format. The use of panels can be enforced to prevent secondary findings.

Filtering

The query system allows to create rules (filtering conditions) on each of the VCF fields. The rules can be logically group together. Disease specific filtering strategies can be prepared to allow for different modes of inheritance (e.g. dominant, recessive) and expected frequency in the population.

Query status

Once the query is submitted its status is visualized. For each filtering strategy there are three queries running:

• count: the query counts of all variants meeting the criteria
• variants: the query returns the first 2000 variants meeting the criteria
• coverage: the query returns all the problematic regions within the selected virtual panel

Query result

By clicking on the banner close to the variants or coverage query statuses, the results can be explored.

Variant details

By double clicking on a variant relevant information is visualised in a summary panel

Sequencing reads visualization

By clicking on the Reads panel a genome browser is shown in order to investigate sequencing and alignment quality

Disease focus

Disease context specific analysis of a patient enables the clinical assessment of variants for the selected disease(s). Previous variant annotations are displayed and highlighted depending on the disease focus. For a given patient it is possible to specify a phenotype by clicking on the clincal curation icon

Variant curation

DART supports the ACMG-AMP annotation of variants in the disease context. Variant annotations are stored in DART as a knowledge base and provided as guidance across samples and diseases.

The variants can be both annotated for quality by clicking on the VALIDATION column, in which case the annotation is specific for the variant, the sample and the vcf file or by clincal significance by clicking on the ANNOTATIONS column, in which case the annotation is specific for the variant and the selected phenotype.

Validation curation

Pathogenicity curation

Visualization of annotated variants

Report generation

Once the curation activity is complete, a report can be generated by clicking on the disk icon.

Please, note that both the panel preset (even if empty) and the query preset must be saved and given a name by clicking on the respective "hearth" icon:

Saving a report can take some time since all the variants and coverage results are saved permantently in the SQL database. It is highly recommended to narrow the filtering to a specific gene panel to save storage and time.