Our tutorials are a popular resource for prospective users. We have added a tutorial to help introduce customers to the ease and utility of the ACMG Guidelines incorporated in VSClinical. The ACMG Guidelines are a collection of 33 criteria that are used to determine a variant’s level of pathogenicity. VSClinical and VarSeq make it easy for users to sort and… Read more »
We have recently added a tutorial to help introduce customers to the ease and utility of the AMP Guidelines incorporated in VarSeq’s VSClinical package. The AMP Guidelines allow users to sort through available clinical evidence in a streamlined fashion to arrive at final classification and interpretation and then transfer that information into a clinical report. And the AMP Guidelines also… Read more »
The common approaches to detecting copy number variants (CNVs) are chromosomal microarray and MLPA. However, both options increase analysis time, per sample costs, and are limited to the size of CNV events that can be detected. VarSeq’s CNV caller, on the other hand, allows users to detect CNVs from the coverage profile stored in the BAM file, which allows you… Read more »
Before examining the clinical evidence associated with a specific mutation, a clinician must establish that the variant is likely to be a driver mutation which generates functional changes that enhance tumor cell proliferation. Our recent blog series “Following the AMP Guidelines with VSClinical” briefly mentioned how the oncogenicity scoring system in VSClinical could be used to automate and assist the… Read more »
VSClinical users can interpret and report genomic mutations in cancer following the AMP guidelines which we’re demonstrating in this “Following the AMP Guidelines with VSClinical” blog series. Part I introduced the hands-on analysis steps involved in creating a high-quality clinical report for targeted Next-Generation Sequencing (NGS) assays. We reviewed sample and variant quality, including the depth of coverage over the target regions by the sequencing performed for each sample. Now, we are ready to… Read more »
In the world of genomics shaping precision medicine in oncology, the limiting factor is the time-to-sign-out of a fully interpreted molecular profile report. There are many components of the entire testing process that add to the turn-around time of each test. Many of these steps, such as sample prep, sequencing, and automated secondary analysis, are bounded and consistent in their time requirements. The hands-on… Read more »
With the increasing knowledge of mutations involved in cancer, it is imperative to have a tertiary analysis pipeline that provides users with the most up to date information on somatic mutations. VSClinical’s Cancer Add-On does just that and more; with this feature, users can investigate and report on SNVs, indels, CNVs, gene fusions, and considerations for wild type genes in… Read more »
Huntington’s Disease (HD) Background Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disease that is caused by a mutation in the huntingtin (HTT) gene resulting in 36 or more CAG trinucleotide repeats in exon 1. Individuals affected by HD experience motor disorders including involuntary movements and poor coordination, cognitive impairments showing a decline in thinking and reasoning and psychiatric disorders… Read more »
Congenital Myasthenic Syndromes (CMS) History: Congenital Myasthenic Syndromes (CMS) are a group of rare hereditary conditions that can cause seizures, severe muscle weakness, respiratory problems, and potentially disabling weaknesses shortly after birth or early childhood (1). CMS is the result of abnormalities in acetylcholine proteins residing in the motor endplate of the neuromuscular junction (1). These abnormalities can be diagnosed… Read more »
Hypertrophic Cardiomyopathy History It was December 9th, 1989, when one of Loyola Marymount’s strongest inside players, Hank Gathers, collapsed during the middle of a collegiate level basketball game against UC Santa Barbara. Measuring in at 6’7” and weighing 210 pounds, Gathers was diagnosed with exercise-induced ventricular tachycardia, or in layman’s terms, an abnormal heartbeat. Even with the concerning nature of… Read more »
Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants Detecting cancer at an early stage can make it much more treatable. Developing tests and making them clinically actionable is crucial to beat this disease. This eBook covers the state-of-the-art gene panel tests for cancer. Of course, there is more that can be done. The field is… Read more »
We are upgrading all VSClinical +Cancer Add-On purchases to a 15-months license! The individualized nature of tumors requires genomic testing for providing the best outcomes for patients. Next-Gen Sequencing enables the detection of small mutations, copy number changes, and common fusions affordably and with high precision. However, the interpretation of these detected variants is arduous without a comprehensive analytical workflow… Read more »
Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants Somatic variants can manifest in different ways: There is a difference between the interpretation of germline and somatic variants. The former is exclusively focused on establishing the level of pathogenicity vis a vis a particular disease. In contrast to that, when we assess the clinical implication of… Read more »
Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants As described in my eBook “Genetic Testing for Cancer,” any bioinformatic pipeline for cancer ultimately calls variants based on the aligned reads that the sequencer generated. Variant calling is the process of reviewing a sequence alignment, typically in the form of a BAM file, to identify loci… Read more »
Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants Analogous to the ACMG guidelines for germline mutations, the Association for Molecular Pathologists (AMP) has issued guidelines to assess and report on somatic variants. The key paper in this area was published by Li et. al (2017) with the title “Standards and Guidelines for the Interpretation and… Read more »
Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants Precision Medicine uses genetic information from individual patients. This may include the following areas: Specifically, in the cancer space, data derived from Next-Gen Sequencing (NGS) is used to diagnose and prognose diseases, select a targeted therapy and potentially evaluate the suitability of a patient to be part… Read more »
Overview VSClinical enables users to evaluate variants according to the ACMG guidelines in a high-throughput fashion and obtain consistent results and accurate variant interpretations. This feature is tightly integrated into our VarSeq platform as well, and when paired together, users can evaluate NGS data and obtain clinical reports all in one suite. Coupled with the ability to find novel or… Read more »
VSClinical provides a rapid-fire way to investigate any variant’s impact by following the ACMG Guidelines process for classification. We will be demonstrating this by looking at interesting examples of rare disorders and showcasing some evaluation steps users may deploy in their analysis. Our first example in this blog series is for a patient who has an indifference to pain, while… Read more »
Examples of Clinical Variant Interpretation with VSClinical In this chapter, I’d like to go through a few examples for variants that have been classified with the help of VSClinical. This will give you a better understanding of how data sources are actually being represented in the software and how those are used to make decisions on applicable criteria. It goes… Read more »
Rules for Combining Various Classification Criteria Now that we have a solid understanding of how the various criteria are meant to be applied, it’s time to look at how the evidence collectively leads to the clinical categorization of a variant. Let’s go through the rule framework for combining the various criteria. Pathogenic In order for a variant to be classified… Read more »
