Category Archives: Clinical genetics

CNV Specific Updates to VarSeq 2.6.0

         May 6, 2024

The recent release of VarSeq 2.6.0 was filled with so many customer-requested features (for example, our long-awaited PGx workflow!) that some of our other new features have not yet had their time in the spotlight. For this blog, we are thrilled to announce that with the release of VarSeq 2.6.0, we have made WGS CNV calling more user-friendly than ever… Read more »

Computed Fields in VarSeq: The ultimate customization tool

         April 2, 2024

Bioinformatic freedom is core to the user experience with Golden Helix software, a topic with which you will be well-versed if you’ve kept up on our recent blogs. We are constantly endeavoring to provide our users with powerful tools to tackle complex and impactful next-generation sequencing (NGS) workflows while maintaining transparency and the ability to customize and augment each component… Read more »

Using Liftover to Curate GnomAD v4 for GRCh37

         January 25, 2024

We are excited to announce the release of our gnomAD v4 annotation tracks for VarSeq. This version of the GnomAD database represents a significant leap forward, including data from an impressive cohort of over 800,000 individuals — a remarkable 5x expansion compared to the previous releases. Notably, this dataset is comprised of two distinct callsets: exome sequencing data from 730,947… Read more »

Evolution of Multi-Allelic Calls in VarSeq: Before and After Version 2.5.0

         November 9, 2023

It may come as a surprise to our long-standing users that the multi-allelic import and representation in VarSeq is slated to have different import options with the 2.5.0 upgrade. As the software grows and evolves, we strive to meet the changing needs of our users, and this is one area where an update was sorely needed. Before going into an… Read more »

Evaluating DeepMind’s AlphaMissense Classifier

         October 20, 2023

Last month, the researchers at Google DeepMind announced the release of AlphaMissense, a new missense prediction algorithm that leverages the protein structure prediction model AlphaFold to distinguish between benign and pathogenic missense variants (Cheng et al., 2023).  AlphaFold is a model for the prediction of protein structures from amino acid sequences. During the development of AlphaMissense, the AlphaFold model was… Read more »

Using Compute Functions to Validate Variant Assessments

         September 26, 2023

Recently, a Golden Helix customer reached out to support for advice on how to validate the variant scoring between two different VarSeq users. Here we break down one possible solution as an opportunity to showcase the utility of both the Latest Sample Assessment function and an alternative way to leverage the Compute Fields function. To set up this validation project,… Read more »

Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer

         July 25, 2023
Felix Mitelman

While the analysis of gene fusions is crucial for understanding the genetic basis of cancer, the process of interpreting these mutations can be challenging. One important component of fusion interpretation is the identification of relevant publications. To aid researchers in the search for publications related to specific gene fusions, Felix Mitelman, and colleagues have created the Mitelman Database of Chromosome… Read more »

Optimizing the Capture of Tier II Evidence in VSClinical AMP

         July 18, 2023

VarSeq 2.3.0 unleashed a whole new way to select, process, analyze, and report cancer variants through complete workflow automation, application of evaluation scripts, and enhanced annotation. Single nucleotide variants, copy number variants, structural variants, and genomic signatures could be added to a single patient evaluation, and Golden Helix CancerKB came packed with new report-ready interpretations to support them! Soon after,… Read more »

When Negative Findings are a Good Thing to Report: Leveraging VarSeq’s VSClinical AMP

         May 25, 2023

Explore the importance of negative findings in genomic medicine through the lens of VarSeq’s VSClinical AMP. When analyzing a somatic sample in VarSeq, users have the option to report on several types of biomarkers with VSClinical AMP. In addition to your usual mutational biomarkers such as small variants, your copy number variants, and structural variants, we support the analysis of… Read more »

Transitioning to Broad-Scale Genomics: From Gene Panels to Whole Genome Sequencing

         May 16, 2023

Explore the evolving landscape of genomic analysis, transitioning from targeted gene panels to whole genome sequencing. A recent trend with our customers has been to expand their workflows from small panel sequencing analyses to larger whole exome and genome sequencing analyses. The decreasing cost of sequencing has made this a rather common request. Although more data allows for a greater… Read more »

Managing the Scope of Somatic Variants Reported in VSClinical

         April 13, 2023
Managing the Scope of Somatic Variants Reported in VSClinical

Discover the power of VSClinical’s Interpretation Match Behavior options for managing the scope of somatic variants in cancer reporting, enabling clinical teams to make informed treatment decisions. Multiple interpretations can apply to a single biomarker or tumor type. In some circumstances, a clinical team may only want to report the most relevant and significant biomarker, treatment, diagnosis, or prognosis interpretations… Read more »

Maximizing Structural Variant Detection with Soft Clip Visualization

         March 27, 2023

Discover how soft clip visualization can help you identify structural variants in your research and improve the accuracy of your findings. Soft clipping is a common technique in sequence alignment used to remove bases from the ends of reads that do not align with the reference sequence. Removing these bases typically improves alignment accuracy. However, when multiple reads are soft… Read more »

Decoding Complex Fusion Representations: A Deep Dive into VCF Breakend Notation and its Impact on Gene Analysis

         March 14, 2023
Decoding Complex Fusion Representations A Deep Dive into VCF Breakend Notation and its Impact on Gene Analysis Icon

Unlocking the intricacies of fusion representations is crucial for understanding the impact of complex genetic rearrangements on gene function and disease development. In the most recent release of VarSeq, we added support for the import of complex rearrangements from VCF files, which typically encode rearrangements using breakend notation. This powerful notation is capable of describing the full spectrum of structural… Read more »

Unlocking Clinical Evidence: A Deep Dive into the Supporting Data Sources of VSClinical AMP Workflow

         February 7, 2023
Unlocking Clinical Evidence: A Deep Dive into the Supporting Data Sources of VSClinical AMP Workflow Icon

Discover the innovative clinical evidence search of the VSClinical AMP workflow, where patient biomarkers and tumor types are matched to the most relevant data from top sources like CIViC, DrugBank, and Clinical Trials. One of the core features of the VSClinical AMP interpretation workflow is the ability to search third-party data sources to find clinical evidence that matches the patient’s… Read more »

Exploring the CRAM File Format in VarSeq 2.3.0

         January 17, 2023

Unlocking the Potential of CRAM Files: The New VarSeq 2.3.0 Release for Enhanced Plotting, Coverage Analysis, and CNV Detection The CRAM (Compressed Reference-oriented Alignment Map) file format was conceived in 2011 as a more space-efficient way to store alignment data. It saves space over the previous standard BAM (Binary Alignment Map) by only storing the differences between each read and… Read more »

Streamlining Variant Analysis for Large Genetic Cohorts: Part 2

         November 29, 2022
Streamlining Variant Analysis for Large Genetic Cohorts: Part 2

The last blog in this series covered streamlining variant analysis for large genetic cohorts, namely case-control studies, on a single-project basis. The reality when dealing with big data is that you often do not handle a high volume project all at once. Therefore, we will follow up on the topic of cohort analysis by discussing Golden Helix’s solution for streamlining… Read more »

Handling a Variety of CNV Caller Inputs with VarSeq – Webcast Recap

         July 19, 2022

First, thank you to everyone who joined us for our recent webcast, Handling a Variety of CNV Caller Inputs with VarSeq. Also, we would like to thank those that Tweeted #CNVsupport @GoldenHelix or emailed us (mmarks@goldenhelix.com) to throw in their questions. This was a successful trial run, and we would like to continue engaging with our users through these outlets…. Read more »

What’s Coming to VSClinical: Expanded Clinical Trial Search Results

         May 17, 2022
Expanding-Clinical-Trial-Search-in-VSClinical

While the interpretation of germline variants generally focuses on the pathogenicity of a variant for a specific disease, the interpretation of somatic variants is centered around each variant’s impact on clinical care. As a result, clinical trials play an important role in assessing the clinical significance of somatic biomarkers, with the AMP Guidelines assigning a higher level of evidence to… Read more »

Reporting Secondary Germline Variants in VSClinical AMP

         March 2, 2022
Reporting Secondary Germline Variants in VSClinical AMP

Tumor profiling via next generation sequencing (NGS) often reveals secondary germline variants that may constitute important incidental findings. In May 2021, the American College of Medical Genetics and Genomics (ACMG) released an updated policy statement for reporting incidental findings in exome and genome sequencing data along with a corresponding list of genes. These recommendations state that laboratories should report pathogenic… Read more »

Selecting Clinically Relevant Transcripts in VarSeq

         June 28, 2021

One of the many tricks of encoding so much functionality into so little space in eukaryotic genomes is the ability to produce multiple distinct mRNAs (transcripts) from a single gene. While one transcript is often the dominant one for a given tissue or cell type, there are, of course, exceptions in the messy reality of biology. It doesn’t take many… Read more »