The VarSeq CNV calling algorithm, VS-CNV, is a powerful tool for calling CNVs from the NGS coverage data stored in your BAM files. However, before this algorithm can be deployed in a clinical setting, it must be tuned and validated using data that is representative of your lab’s NGS workflow. In the past, this validation process could be difficult, as… Read more »
Clinical diagnostic efforts in next-generation sequencing are commonly defined at a gene panel level. The validation process of adding new genes to any diagnostic panel is ongoing, but labs typically construct and validate their clinical workflows for the current status of verified genes. This is not limited to primary finding results but can also include any incidental findings among the… Read more »
Clinical labs often maintain gene panels, which are lists of genes with evidence of disease association. These panels are used to prioritize variants and limit interpretations to a predefined set of test-specific genes. In general, gene panels should be stored independently of any specific project or interpretation, as it is common for an individual gene panel to be generally applicable… Read more »
Thanks for checking out this blog on how to to get more out of your VarSeq projects! The best way to show off one of my favorite new features that have been incorporated into the latest VarSeq 2.2.3 release is with a scenario: You work in a lab that processes and analyzes multiple whole exome samples for copy number variations,… Read more »
Thank you to those who attended the recent webcast, “High Precision Exome CNV Detection with VS-CNV”. For those who could not attend but wish to watch, here is a link to the recording. This webcast delved into the complex world of CNV calling for whole-exome samples, which presents unique challenges that require specific considerations and strategies. Over the past several months,… Read more »
In many cases, VarSeq users design their next-gen sequencing workflows for a clinical application. One of the major values of using VarSeq is the standardization of sample analysis via project templates for filtering down to rare variants and isolate any clinically relevant variant. However, VarSeq also doubles as a robust research application as well. There are specific algorithms that can… Read more »
While VarSeq has always had excellent support for variant interpretation and analysis, we continue to find new edge cases in the clinical literature that improve our interpretation capabilities. In this blog, we will be covering some of the new improvements in VarSeq to support the interpretation of non-coding and splice site variants. Transcript Annotation Improvements Let’s start by covering some… Read more »
Orphanet is a public database available in VarSeq that aims to improve the current understanding and treatment options for patients affected by rare diseases. This resource was established in France in 1997 and has gradually grown to cover a consortium of over 40 countries in Europe. The primary goal of this database is to provide a universal nomenclature to classify… Read more »
Clinical testing labs produce reports as the end product of the NGS variant detection and interpretation workflow. Necessarily, the content, detail, and presentation of the report needs to be specialized to each clinical lab, and potentially each offered test. Our last blog post introduced the new Word-based report templates in VSClinical. In this blog post, we will introduce and explore… Read more »
The collaboration between the Clinical Genome Resource (ClinGen) consortium and the American College of Medical Genetics (ACMG) recently developed published guidelines for the interpretation of CNVs called on next-generation sequencing data. These new guidelines are the first to provide a robust set of rules for the interpretation of small intragenic deletions and duplications and are now automated in VSClinical. … Read more »
In many cases, VarSeq users typically run single trio projects or perhaps an extended family project. Not only are all the inheritance model algorithms available in the VarSeq software to capture de novo, dominant, or recessively inherited variants but there are a number of quality control fields to help ensure the pedigree was set up properly. The last thing any… Read more »
The recent release of VarSeq 2.2.2 brings our Word report template system, previously featured in VSClinical AMP, to the VSClinical ACMG workflow. This blog post will describe how to use the Word template system using one of our shipped templates as well as how to start customizing your own templates. We will cover the three different report templates that ship… Read more »
Thank you for attending the webinar focused on implementing VarSeq and VSClinical for family-based workflows. If you would like to use the webinar as a reference or were not able to attend, you can access it using the following link to view ‘Family-Based Workflows in VarSeq and VSClinical. Here is a brief recap of what we discussed: This webinar demonstrated… Read more »
There is a multitude of interesting new features that have been incorporated into VarSeq 2.2.2. In this blog, I want to continue the discussion of these features and how each can be incorporated into your workflow, and also discuss the application of the Probability Segregation algorithm for copy number variation (CNV) analysis. The Probability Segregation algorithm is a new algorithm… Read more »
Our latest VarSeq release is one of the largest we’ve ever had, boasting an extensive list of new features and improvements. As part of this release, we have dramatically expanded our support for splice site analysis. This includes improvements to our novel splice site algorithm and support for splice site effect prediction along with several other small improvements. Novel Splice… Read more »
Our recent release of VarSeq 2.2.2 comes with a long list of upgrades and new features. In this blog post, we will demonstrate how defining sample phenotypes are available in VSClinical. One noticeable change is the ACMG guideline variant evaluation in VSClinical. Not only has this interface added CNV guideline evaluation, simplified the reporting process with embedded Microsoft Word and… Read more »
Golden Helix offers a market-leading bioinformatics solution that allows users to evaluate next-generation sequencing variants according to the ACMG and now ACGS guidelines. The ACMG guidelines were created in 2015 and are widely accepted as best practice for the interpretation of sequencing variants throughout the United States (Richard et al 2015). Very similar are the ACGS guidelines that were developed… Read more »
Curious about how coverage statistics can be used in conjunction with VarSeq? Evaluating the coverage over target regions or whole genomes is essential whether you are working with variant or CNV analysis. VarSeq has had the capability to compute sample level coverage statistics for some time now, but in the 2.2.2 release of VarSeq, there are some new features that… Read more »
In this blog post, I will be analyzing a loss-of-function splice variant in MTHFR using VarSeq. In the search for clinically relevant variants contributing to rare disorders, efficient filtering strategies are an important step in eliminating disinteresting variants. However, any applied filters must also ensure no interesting variants inadvertently get filtered out. Golden Helix provides the tools to complete this… Read more »
In the webcast, Evaluation of Copy Number Variants with VSClinical’s New ACMG Guideline Workflow, we discussed how VSClinical implements Section 4 of the ACMG guidelines. Specifically, we focused on integrating literature and publications to assess the pathogenicity of a CNV event when there was a lack of dosage sensitivity information. One of the primary pieces of evidence for evaluating genes… Read more »
