VSWarehouse Upgrade: Somatic Variant Analysis via VSClinical AMP Workflow

         October 25, 2019

This month’s webcast delves into VSWarehouse with a focus on our new capability of storing somatic variant projects and catalogs built for the AMP Guidelines within VSClinical. If you didn’t have a chance to join us for the live event, please enjoy the video recording below.

Previous webcasts have gone into great detail on the features and processing of somatic variants following the automated AMP Guidelines in VSClinical. A few of these webcasts I recommend checking out are:

Our VSWarehouse VSClinical webcast covers the same AMP project in these previous webcasts but starts off by reviewing the accessibility and usability of VSWarehouse through a browser. As a genomic repository, VSWarehouse provides immense power for tertiary variant analysis. Not only are users able to upload and query through all desired variant/sample data in the repository, but VSWarehouse can also retain the workflow template structure. Having this filtering option makes sifting through a massive cohort of millions of variants possible in mere seconds.

Figure 1 (below) is a great example of a VarSeq filter workflow uploaded to the VSWarehouse browser. The list of annotations and algorithms in the project are accessible on the left side of the screen, where users can set criteria such as clinical significance, general population, and cohort variant frequencies. This example has resulted in four rare but known pathogenic variants.

Figure 1. VSWarehouse based filtering capability built from all annotations and algorithms available from the VarSeq software.

After clicking on the results page, the four filtered variants are listed and each can be selected to review which samples share the variants, or even exported into a VCF if wanting to reimport into VarSeq for evaluation (Figure 2). Users can modify the preferred columns to quickly examine any necessary variant details and even access direct hyperlinks to associated databases (Figure 3).

Figure 2. Filtered variants resulting from VSWarehouse workflow query.
Figure 3. Custom variant field selection for preferred view in VSWarehouse browser.

Beyond variant filtering, users also are presented with ongoing lists of new variants or variant with updated classifications in ClinVar. This feature is critical for addressing the concern of keeping tabs on variants that will need re-evaluation once more clinical evidence becomes available.

Figure 4. ClinVar variant tracker in VSWarehouse to assist with new variant submissions and changing variant classifications.

From a VarSeq perspective, the Manage VSWarehouse terminal is the access point to upload sample and projects up to Warehouse but is also where users can access the stored data for annotation. A good example of utilizing project data as an annotation (Figure 5) is to leverage cohort frequencies as a filtering criterion in the VarSeq project. Figure 6 shows the integration of an allele frequency filter built from a 1000 sample cohort stored in VSWarehouse, with thresholds set to capture variants present < 30% or missing from the cohort.

Figure 5. VSWarehouse terminal is the hub to upload new project, reports, and catalog data, and is also the access to annotate against project data to filter common variants seen in cohort.
Figure 6. Allele frequency filter accessed from cohort data in VSWarehouse and integrated into VarSeq workflow.

Following the filter chain results, users will select the variants to be reviewed through the VSClinical AMP Guidelines. Once opening the VSClinical tool in VarSeq, users work toward not only processing the somatic oncogenicity score, but also review any available treatment options for the biomarker and finally render an automated clinical report from all captured interpretations and related data. The capture of the final interpretations for these biomarkers is in an assessment catalog built specifically for the AMP Guidelines. VSWarehouse now supports the creation of these somatic catalogs (Figure 7) which reinforces the consistency and comprehensiveness of variant classification and interpretation. Essentially, users can access these catalogs simultaneously from their Warehouse so to centralize the continuous capture of all variant knowledge among all users.

Figure 7. VSClinical based assessment catalogs accessed directly from the VSWarehouse repository.

This is a quick overview of what you will learn from this webcast. We hope you enjoy following along as we covering these details and discuss general VSWarehouse concepts and values, but also explore the upgraded support of VSClinical AMP Guidelines. If you have any specific questions you would like to be addressed about the content of the webcast, please enter them in the comments box below or email us at info@goldenhelix.com!

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