Evaluation Script Adding Variants to Catalog

         April 23, 2024

Variant curation is one of the most important aspects of a next-generation sequencing workflow. The routine application of previously rendered interpretations, paired with the ability to take into account evolving knowledge bases, allows clinical practices to rapidly and accurately provide life-saving results to patients. Hence, assessment catalogs, versatile databases that store variant interpretations for rapid access, form one of the pillars of NGS analysis with Golden Helix’s software stack. True to our core values, automation in tandem with transparent workflows plays a key role here.

VarSeq and VSClinical, the fundamental components of the Golden Helix software stack, work by bringing all of the available information to users’ fingertips while leaving the final judgment call on variant classification and interpretation to users’ expertise. Assessment catalogs provide the infrastructure for saving and viewing these interpretations and follow the same guidelines regarding user input and automation. Let’s break down how assessment catalogs might hypothetically fit into a VarSeq workflow and then explore how to implement various levels of automation.

In general, we can categorize variants into three categories, though, of course, more nuanced distinctions exist: (1) obvious pathogenic or oncogenic variants, (2) variants of uncertain significance (VUS), and (3) obvious benign variants. While VarSeq can be configured to provide suggestions on which category a given variant falls into, we leave the ultimate delineation to the experts, i.e., our users. Wherever users choose to draw the line between these classifications, assessment catalogs are a quintessential tool for keeping track of each class of variants. A single assessment catalog can be used to capture data on all variants, and later used to compare new samples to existing interpretations, or users can parse out sub-types of variants into different catalogs.

Regardless of how users choose to distribute their interpretations, assessment catalogs have a compounding effect on streamlining analysis down the line. Previously interpreted obvious pathogenic or oncogenic variants can be reported immediately, predetermined benign variants can be filtered out of the workflow, and VUS variants can be saved for later and routinely audited for changes in classification. All of these utilities can be implemented into a custom VarSeq workflow or accessed through assessment catalogs’ integration into VSClinical, further empowering users to decide what works best for their use case.

So far, we’ve talked abstractly about how assessment catalogs can be used. Excitingly, with all of the nuance intact, all of these capabilities can be carried out manually or automated. Specifically, evaluation scripts in VSClinical can be fully customized to categorize and sort variants based on users’ specifications. For example, one could use an evaluation script to automatically remove benign variants from an evaluation and store variants of uncertain significance, leaving only the important work of analyzing and reporting potentially pathogenic or oncogenic variants to the end user. The intrepid VarSeq user can check out our blog on integrating VSClinical evaluation scripts into VSPipeline workflows to see how automating assessment catalog actions can be even more streamlined.

Overall, users will find VarSeq rife with tools for streamlining and customizing workflows, fully complemented by the automation tools to kick everything into gear as labs scale up their VarSeq usage. Our FAS team loves saving time for our users, so please don’t hesitate to reach out to support@goldenhelix.com to talk automation and optimization!

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