Category Archives: Best practices in genetic analysis

GnomAD v4 Released: Enhanced Data and Golden Helix Curation for VarSeq Users

         February 7, 2024

The Broad Institute’s release of gnomAD v4 needs no introduction as the data in this release is highly sought after by professionals in the genetics community, and the v4 release has a lot to boast about! The v4 release is roughly five times larger than the v2 and v3 releases combined and includes data from 807,162 total individuals. Naturally, exome… Read more »

Advanced Techniques for GenomeBrowse Customization

         January 23, 2024

Today, we will be exploring the indispensable role of GenomeBrowse in your VarSeq workflows. This blog aims to guide you through various customization options, including color preferences, filtering techniques, display modifications, numeric value plotting, and additional tips. I hope to enhance your GenomeBrowse experience and enable you to gain valuable insights into your data. Let’s jump in by talking about… Read more »

Food Allergy Alleles, Right in Time for Thanksgiving!

         November 21, 2023

The table is set, the football game is on in the background, and the family has gathered around the table when out of nowhere, your Cousin Eddie shows up for Thanksgiving dinner. While Cousin Eddie is known for eating anything, his allergies always get the best of him, ruining the evening. Thankfully, this year Cousin Eddie had recently gotten his… 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 »

Choosing Bin Sizes for the VarSeq CNV Binned Caller

         September 14, 2023

Detecting CNVs from whole genome data has a number of advantages but also unique challenges. Whole genomes offer a comprehensive and uniform picture of the entire genome, allowing a user to capture CNVs at a higher resolution than with data sequenced at a lesser scale. It also allows for the detection of structural variation over non-coding regions and for a… Read more »

Get More Out of Assessment Catalogs by Storing and Tracking Variant Artifacts

         August 8, 2023

Assessment catalogs are a way for VarSeq users to save variants and variant information for clinically relevant variants, so when you come across this variant again in another sample, all of the work to analyze and classify the variant is already done! But there is more than meets to the eye when it comes to using assessments in VarSeq. Being… Read more »

Using Evaluation Scripts to Automatically Incorporate Secondary Evidence into Your AMP Workflow

         June 15, 2023

The AMP guidelines workflow in VSClinical provides a user-friendly tool for the interpretation of somatic biomarkers across the entire spectrum of genomic variation. One of the most useful features of this workflow is its ability to streamline the evaluation of clinical evidence for a somatic biomarker using the AMP Tier evidence levels. The AMP Guidelines classify a biomarker into one… 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 »

Getting the most out of variant visualizations in GenomeBrowse

         June 29, 2022

Genomic data visualization is an extremely powerful means to help users comprehend massive amounts of sequencing data and is valuable for communicating genomic information and findings. Genome browser tools allow users to visualize aligned sequence data in BAM format, map the data to a reference assembly, view annotation tracks, genomic region tracks, export graphics for sharing, and much more. Genome… Read more »

Merging VCFs in an Imperfect World

         September 7, 2021

Merging variant records, VCFs, across samples is important when performing trio or family analysis as it ensures that hereditary relationships can be properly inferred. There are many ways to represent a single variant. Insertions and deletions may be right or left aligned, prefixes and suffixes can be added, and adjacent variants in the same sample may be combined or split… 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 »

Highlights from our PhoRank 2.0 Webcast

         June 10, 2021

Thank you to those who attended our recent webcast, “PhoRank 2.0: Improved Phenotype-Based Gene Ranking in VarSeq”. For those who could not attend, you can find a link to the recording here. This webcast covered upcoming improvements to the PhoRank phenotype-based gene ranking algorithm based on literature published in the years since the algorithm’s development. The PhoRank Algorithm When performing… Read more »

Variant Filtration and Interpretation

         June 3, 2021

I learned about Batten disease from a childhood friend’s Facebook post. Over the course of a few months, her 8-year-old, Eva, the oldest of 4 daughters – Emily, Lucy, and Carly – was rapidly going blind. Baffled, doctors ran a genetic panel that returned a devastating result – the diagnosis of Juvenile Neuronal Ceroid Lipofuscinosis or Batten disease. A broad… Read more »

Case Study – Hannover Medical School

         May 11, 2021
hannover

Dr. Auber is the team leader for the molecular genetic diagnosis of hereditary diseases at the Institute for Human Genetics at Hannover Medical School (MHH). MHH is one of the largest hospitals in northern Germany, with one of the largest outpatient clinics for individuals and families dealing with hereditary cancer and predisposition syndromes. Dr. Auber was in high school when… Read more »

VarSeq NGS Workflow Design: Clinical vs. Research

         April 22, 2021
NGS Clinical Research

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 »

VarSeq Update: Support for the Interpretation of Non-coding and Splice Site Variants

         April 15, 2021
Splice site

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 »

New Assessment Catalogs Improve Saving and Tracking Variant Interpretations

         March 23, 2021

In this blog, we will be covering new assessment catalogs and how they work to improve saving and tracking variant interpretations. VarSeq is a variant analysis tool that effectively analyzes single nucleotide (SNVs) and copy number variants (CNVs) in both cancer and germline workflows.  Because VarSeq enables such diverse variant analysis, there are many research labs and institutions that evaluate… Read more »

New Mendel Error Algorithm in VarSeq

         March 2, 2021
mendel algorithm

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 »

New CNV Tools with VarSeq 2.2.2 Update

         February 16, 2021
copy number variant algorithm

Our latest release of the VarSeq software has had a major upgrade with the addition of the new CNV ACMG guidelines! Here are some recent webcasts we’ve given covering the new guideline tool: Family-Based Workflows in VarSeq and VSClinical A User’s Perspective: ACMG Guidelines for CNVs in VSClinical Not only does VarSeq 2.2.2 come with the new guideline tool, but… Read more »