Clinical Validation of Copy Number Variants Using the AMP Guidelines
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This document discusses Golden Helix's software for clinical variant analysis and summarizing copy number variants using American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) guidelines. It acknowledges funding support from several National Institutes of Health grants. It also lists upcoming discussion sessions on applying ACMG/AMP guidelines in clinical practice and analyzing copy number variants from next-generation sequencing data.
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Clinical Validation of Copy Number Variant Detection by Next-Generation Seque...
Despite the great advances achieved in clinical genetics thanks to the incorporation of NGS (Next Generation Sequencing), a significant percentage of patients with diseases of genetic origin still do not have a conclusive molecular diagnosis. The incorporation of state-of-the-art bioinformatic methods has allowed the implementation of CNVs (Copy Number Variants) detection in NGS analysis, improving its diagnostic efficiency. In this study, the clinical utility of the detection of CNVs by NGS has been proven.
During 2018, 275 patients were studied using the NGS technique without obtaining an accurate genetic diagnosis. Bioinformatic tools that compare the normalized sequencing depth between patients and controls were used to determine CNVs. The results obtained were compared with patients own laboratory database and controls to rule out polymorphisms and false positives. All causal CNVs were confirmed by MLPA.
Pathogenic CNVs causing the disease were detected in 11 of the 275 patients (4%). Specifically, CNVs were detected for pathologies with autosomal dominant inheritance patterns (TSC2, MSH2, and FBN1), as well as for genes with autosomal recessive inheritance patterns, including two homozygous deletions (KCNV2 and RDX) and one heterozygous deletion with an SNV (Single Nucleotide Variant) in the PKHD1 gene. One of the most notable cases corresponds to a patient suspected of hypomagnesemia in which two deletions were identified in compound heterozygous mutation in the TRPM6 gene.
Evaluating Copy Number Variants with VSClinical's New ACMG Guideline Workflow
Golden Helix has been in close communication with the publishers of the ACMG guidelines and the ClinGen group to receive expert advice on how to interpret CNVs called on NGS data. These guidelines provide a robust set of rules for interpreting intragenic deletions and duplications, which is summarized into an intricate decision tree that is broken down into 80 distinct criteria. This complexity is further compounded by many important caveats, exceptions, and considerations known to many in the CNV clinical workspace but are not mentioned in the published guidelines. Fortunately, Golden Helix has spent long hours reading the guidelines, watching the webinars, reading the supplementary material, and working with collaborators to develop a comprehensive workflow to guide you through your clinical interpretation of CNVs. Herein, we are excited to cover more details into this novel ACMG CNV guideline interpretation workflow and demonstrate how intuitive this feature can be for your clinical pipeline. Specifically, we will cover:
The intricacies of the ACMG CNV Sample auto classifier
Unique annotations and algorithms
Adjustable metrics and parameters in the VSClinical ACMG interface
Rendering clinical reports
An Exploration of Clinical Workflows in VarSeq
In this webcast, we feature several example workflows and helpful features in the VarSeq that can be used in the clinic. We discuss options for conducting a comprehensive gene panel analysis for cancer or hereditary diseases. Then we introduce an example of a single exome workflow that goes from an unfiltered VCF created by a secondary analysis pipeline to a report containing information about interesting variants. Finally, we walk through an example of a trio analysis showcasing a variety of different filter options as well as inheritance patterns. All these workflows will result in a customizable clinical report.
Evaluating Oncogenicity in VSClinical
Before assessing the clinical significance of a somatic mutation, one must determine if the mutation is likely to be a driver mutation (i.e. a mutation that provides a selective growth advantage, thereby promoting cancer development). To aid clinicians in this process, VSClinical provides an oncogenicity scoring system, which uses a variety of metrics to classify a given somatic mutation into one of the following categories: oncogenic, likely oncogenic, benign, likely benign, or uncertain significance. This scoring system is heavily inspired by the ACMG Guidelines for the interpretation of germline mutations but has several important differences to make it more applicable in the context of somatic variant interpretation.
Our oncogenicity scoring system relies on an additive point system in which points are assigned to a given variant based on several criteria. Many of the criteria are shared by the ACMG Guidelines for germline variant interpretation, such as population frequency information, variant effect on protein function, and nearby pathogenic variants in catalogs such as ClinVar. However, other criteria are specific to the world of somatic variant interpretation. These include the variant’s presence in somatic catalogs such as COSMIC, the effect of other known oncogenic variants in the same gene, and the variant’s presence in known cancer hotspots or active binding sites. These criteria are combined by summing over the scores for all applicable scoring criteria. Scores exceeding 3 indicate an oncogenic or likely oncogenic classification, while scores falling below -3 indicate a benign or likely benign classification.
In this webcast, we discuss how each of these scoring criteria are combined to obtain an oncogenicity classification. This includes a discussion of the considerations taken into account during the development of this scoring system and a detailed analysis of several example mutations to illustrate the system in practice.
A User’s Perspective: ACMG Guidelines for CNVs in VSClinical
Our last webcast introduced the newest features of VarSeq that will be included in our upcoming release. After a serious developmental effort, we are excited to announce one of these being the integration of ACMG Guidelines for CNVs!
VarSeq is not only the tertiary environment to filter through your imported SNVs and indels from any VCF file, but also includes robust and proven capabilities of CNV detection and clinical variant interpretation. With our upcoming release, users will be able to leverage an automated CNV ACMG classification filter that is paired with the CNV evaluation in the VSClinical interpretation hub. This webcast will expose attendees to literature reinforcing the quality of our CNV caller, as well as showing examples of CNV analysis to demonstrate how this tool can streamline the analysis process. In this webcast, we will cover:
Describing the new CNV guidelines and how Golden Helix tackles their complexity
Assessing CNV impact on Gene and Gene Dosage
Cited literature referencing the accuracy of VarSeq’s CNV calling
Product demonstrations of VSClinical’s CNV interpretation/classification and final report functionalities
Manually traversing the guidelines and classification process is fundamentally complex with multiple criteria considerations, collecting any necessary caveats, and bulk literature review just to name a few. It is our goal to simplify and streamline this process without losing user-control of final results or overlooking any crucial criteria components necessary for final classification. We hope you will join us to see how this is accomplished as we explore the ACMG CNV Guidelines within VSClinical from the user’s perspective!
Utilization of NGS data and genomic selection to rescue an endangered and her...
The Florida Cracker Sheep (FCS) is one of the oldest sheep breeds in the United States. This heritage breed from Florida, naturally adapted to humid and hot climate conditions, is one of the most parasite resistant breeds from the Southern US. However, approximately 1,000 individuals remain alive in the world. Therefore, more research and conservational efforts are required to support all the FCS producers from Florida and rescue FCS from extinction.
Advancements in NGS technologies and reduction in genotyping costs have allowed the utilization of these tools in animal genetics and genomics. We followed up a FCS population (n = 350) from a commercial farm to evaluate parasite resistance traits (FEC, FAMACHA score, hematocrit) using a longitudinal study and genotyped 300 sheep using the GGP Ovine 50k array. Analysis with Golden Helix SVS software identified 15 SNPs with additive and non-additive effects associated with parasite resistance in chromosome 1, 2, 3, 6, 8, 10, 11,12, 13 and 21. Also, a deletion CNV was associated with parasite resistance (FEC) in chromosome 21. Some of these DNA variants were located in STAT5B, NRIPI, TRPM3, WC1, GPC5, CELF2 and RAB3IL genes which control immune response mechanisms in sheep.
Validation of these results and implementation of genomic selection utilizing information from NGS, SNP genotyping and WGS can be easily performed by Golden Helix SVS software. This will allow the implementation of breeding and conservational programs in FCS farms and will improve the profitability of farms over the long term by incorporating the use of genetically parasite resistant sheep and promote local sheep meat production in Florida.
Next-Generation Sequencing Analysis in VSClinical
VarSeq is a tertiary analysis platform that allows users to filter and annotate NGS sequencing data to identify clinically relevant variants. Following this workflow, VSClinical can then be used to automate both germline and somatic variant analysis in accordance with the ACMG and AMP guidelines by using a variety of functional prediction models and clinical and reviewer-based annotations. Once variant or biomarker interpretations are completed, they can be rendered in a customizable clinical report and stored in an internal assessment catalog as an internal variant database repository. Together, implementation of VSClinical will promote increased lab throughput as well as accuracy and compliance with the ACMG and AMP guidelines, which in turn can save time and money. To show the capabilities of our software, this webcast will provide a demonstration of how to use VarSeq and VSClinical for the evaluation of both germline and somatic variants in accordance with the ACMG and AMP Guidelines.
In this webcast, we will cover:
- Filter logics for germline and somatic variants and selecting them into the VSClinical interface
- Capabilities of functional prediction and splice site algorithms for edge case variants
- The functionality of changing the clinically relevant transcript on variant interpretation
- Rendering a clinical report with germline and somatic variants with the inclusion of clinical trials
VSClinical: First Commercial Product to Integrate the Updated ACMG Guidelines...
As CNV detection has become widely adopted as a component of NGS testing, the demand has grown for an interpreting framework specific to CNVs in the context of rare and inherited disorders. Earlier this year, a ClinGen working group in collaboration with ACMG, published new guidelines for the interpreting and reporting of CNVs detected by NGS. We at Golden Helix have been hard at work expanding VSClinical to incorporate these new scoring and evaluation criteria for the interpretation and clinical reporting of CNVs alongside small variants in our popular guided workflow for following the ACMG guidelines. Please join us in this webinar as we preview the upcoming release of VarSeq with this major development. We will cover the following:
- The new CNV guidelines, the specialized criteria for gains and losses, and how VSClinical simplifies the scoring and interpretation process
- How VS-CNV and VSClinical provides a complete solution for clinical detection and interpretation of CNVs for NGS gene panels and exomes
- The number of CNV specific data sources curated and integrated into the automatic recommendation system
- VSClinical’s integrated Word-based template system for designing custom clinical reports that include quality summary information, coverage at exon and gene level, interpreted variants and CNVs, and patient-level results
We are excited to release this major update to VSClinical, incorporating many small feature enhancements and user requests alongside with the integration of the CNV guidelines. Please join us in this webinar to see how CNVs can be an integrated part of the analysis workflow for your clinical NGS tests.
Recommended
Clinical Validation of Copy Number Variant Detection by Next-Generation Seque...
Despite the great advances achieved in clinical genetics thanks to the incorporation of NGS (Next Generation Sequencing), a significant percentage of patients with diseases of genetic origin still do not have a conclusive molecular diagnosis. The incorporation of state-of-the-art bioinformatic methods has allowed the implementation of CNVs (Copy Number Variants) detection in NGS analysis, improving its diagnostic efficiency. In this study, the clinical utility of the detection of CNVs by NGS has been proven.
During 2018, 275 patients were studied using the NGS technique without obtaining an accurate genetic diagnosis. Bioinformatic tools that compare the normalized sequencing depth between patients and controls were used to determine CNVs. The results obtained were compared with patients own laboratory database and controls to rule out polymorphisms and false positives. All causal CNVs were confirmed by MLPA.
Pathogenic CNVs causing the disease were detected in 11 of the 275 patients (4%). Specifically, CNVs were detected for pathologies with autosomal dominant inheritance patterns (TSC2, MSH2, and FBN1), as well as for genes with autosomal recessive inheritance patterns, including two homozygous deletions (KCNV2 and RDX) and one heterozygous deletion with an SNV (Single Nucleotide Variant) in the PKHD1 gene. One of the most notable cases corresponds to a patient suspected of hypomagnesemia in which two deletions were identified in compound heterozygous mutation in the TRPM6 gene.
Evaluating Copy Number Variants with VSClinical's New ACMG Guideline Workflow
Golden Helix has been in close communication with the publishers of the ACMG guidelines and the ClinGen group to receive expert advice on how to interpret CNVs called on NGS data. These guidelines provide a robust set of rules for interpreting intragenic deletions and duplications, which is summarized into an intricate decision tree that is broken down into 80 distinct criteria. This complexity is further compounded by many important caveats, exceptions, and considerations known to many in the CNV clinical workspace but are not mentioned in the published guidelines. Fortunately, Golden Helix has spent long hours reading the guidelines, watching the webinars, reading the supplementary material, and working with collaborators to develop a comprehensive workflow to guide you through your clinical interpretation of CNVs. Herein, we are excited to cover more details into this novel ACMG CNV guideline interpretation workflow and demonstrate how intuitive this feature can be for your clinical pipeline. Specifically, we will cover:
The intricacies of the ACMG CNV Sample auto classifier
Unique annotations and algorithms
Adjustable metrics and parameters in the VSClinical ACMG interface
Rendering clinical reports
An Exploration of Clinical Workflows in VarSeq
In this webcast, we feature several example workflows and helpful features in the VarSeq that can be used in the clinic. We discuss options for conducting a comprehensive gene panel analysis for cancer or hereditary diseases. Then we introduce an example of a single exome workflow that goes from an unfiltered VCF created by a secondary analysis pipeline to a report containing information about interesting variants. Finally, we walk through an example of a trio analysis showcasing a variety of different filter options as well as inheritance patterns. All these workflows will result in a customizable clinical report.
Evaluating Oncogenicity in VSClinical
Before assessing the clinical significance of a somatic mutation, one must determine if the mutation is likely to be a driver mutation (i.e. a mutation that provides a selective growth advantage, thereby promoting cancer development). To aid clinicians in this process, VSClinical provides an oncogenicity scoring system, which uses a variety of metrics to classify a given somatic mutation into one of the following categories: oncogenic, likely oncogenic, benign, likely benign, or uncertain significance. This scoring system is heavily inspired by the ACMG Guidelines for the interpretation of germline mutations but has several important differences to make it more applicable in the context of somatic variant interpretation.
Our oncogenicity scoring system relies on an additive point system in which points are assigned to a given variant based on several criteria. Many of the criteria are shared by the ACMG Guidelines for germline variant interpretation, such as population frequency information, variant effect on protein function, and nearby pathogenic variants in catalogs such as ClinVar. However, other criteria are specific to the world of somatic variant interpretation. These include the variant’s presence in somatic catalogs such as COSMIC, the effect of other known oncogenic variants in the same gene, and the variant’s presence in known cancer hotspots or active binding sites. These criteria are combined by summing over the scores for all applicable scoring criteria. Scores exceeding 3 indicate an oncogenic or likely oncogenic classification, while scores falling below -3 indicate a benign or likely benign classification.
In this webcast, we discuss how each of these scoring criteria are combined to obtain an oncogenicity classification. This includes a discussion of the considerations taken into account during the development of this scoring system and a detailed analysis of several example mutations to illustrate the system in practice.
A User’s Perspective: ACMG Guidelines for CNVs in VSClinical
Our last webcast introduced the newest features of VarSeq that will be included in our upcoming release. After a serious developmental effort, we are excited to announce one of these being the integration of ACMG Guidelines for CNVs!
VarSeq is not only the tertiary environment to filter through your imported SNVs and indels from any VCF file, but also includes robust and proven capabilities of CNV detection and clinical variant interpretation. With our upcoming release, users will be able to leverage an automated CNV ACMG classification filter that is paired with the CNV evaluation in the VSClinical interpretation hub. This webcast will expose attendees to literature reinforcing the quality of our CNV caller, as well as showing examples of CNV analysis to demonstrate how this tool can streamline the analysis process. In this webcast, we will cover:
Describing the new CNV guidelines and how Golden Helix tackles their complexity
Assessing CNV impact on Gene and Gene Dosage
Cited literature referencing the accuracy of VarSeq’s CNV calling
Product demonstrations of VSClinical’s CNV interpretation/classification and final report functionalities
Manually traversing the guidelines and classification process is fundamentally complex with multiple criteria considerations, collecting any necessary caveats, and bulk literature review just to name a few. It is our goal to simplify and streamline this process without losing user-control of final results or overlooking any crucial criteria components necessary for final classification. We hope you will join us to see how this is accomplished as we explore the ACMG CNV Guidelines within VSClinical from the user’s perspective!
Utilization of NGS data and genomic selection to rescue an endangered and her...
The Florida Cracker Sheep (FCS) is one of the oldest sheep breeds in the United States. This heritage breed from Florida, naturally adapted to humid and hot climate conditions, is one of the most parasite resistant breeds from the Southern US. However, approximately 1,000 individuals remain alive in the world. Therefore, more research and conservational efforts are required to support all the FCS producers from Florida and rescue FCS from extinction.
Advancements in NGS technologies and reduction in genotyping costs have allowed the utilization of these tools in animal genetics and genomics. We followed up a FCS population (n = 350) from a commercial farm to evaluate parasite resistance traits (FEC, FAMACHA score, hematocrit) using a longitudinal study and genotyped 300 sheep using the GGP Ovine 50k array. Analysis with Golden Helix SVS software identified 15 SNPs with additive and non-additive effects associated with parasite resistance in chromosome 1, 2, 3, 6, 8, 10, 11,12, 13 and 21. Also, a deletion CNV was associated with parasite resistance (FEC) in chromosome 21. Some of these DNA variants were located in STAT5B, NRIPI, TRPM3, WC1, GPC5, CELF2 and RAB3IL genes which control immune response mechanisms in sheep.
Validation of these results and implementation of genomic selection utilizing information from NGS, SNP genotyping and WGS can be easily performed by Golden Helix SVS software. This will allow the implementation of breeding and conservational programs in FCS farms and will improve the profitability of farms over the long term by incorporating the use of genetically parasite resistant sheep and promote local sheep meat production in Florida.
Next-Generation Sequencing Analysis in VSClinical
VarSeq is a tertiary analysis platform that allows users to filter and annotate NGS sequencing data to identify clinically relevant variants. Following this workflow, VSClinical can then be used to automate both germline and somatic variant analysis in accordance with the ACMG and AMP guidelines by using a variety of functional prediction models and clinical and reviewer-based annotations. Once variant or biomarker interpretations are completed, they can be rendered in a customizable clinical report and stored in an internal assessment catalog as an internal variant database repository. Together, implementation of VSClinical will promote increased lab throughput as well as accuracy and compliance with the ACMG and AMP guidelines, which in turn can save time and money. To show the capabilities of our software, this webcast will provide a demonstration of how to use VarSeq and VSClinical for the evaluation of both germline and somatic variants in accordance with the ACMG and AMP Guidelines.
In this webcast, we will cover:
- Filter logics for germline and somatic variants and selecting them into the VSClinical interface
- Capabilities of functional prediction and splice site algorithms for edge case variants
- The functionality of changing the clinically relevant transcript on variant interpretation
- Rendering a clinical report with germline and somatic variants with the inclusion of clinical trials
VSClinical: First Commercial Product to Integrate the Updated ACMG Guidelines...
As CNV detection has become widely adopted as a component of NGS testing, the demand has grown for an interpreting framework specific to CNVs in the context of rare and inherited disorders. Earlier this year, a ClinGen working group in collaboration with ACMG, published new guidelines for the interpreting and reporting of CNVs detected by NGS. We at Golden Helix have been hard at work expanding VSClinical to incorporate these new scoring and evaluation criteria for the interpretation and clinical reporting of CNVs alongside small variants in our popular guided workflow for following the ACMG guidelines. Please join us in this webinar as we preview the upcoming release of VarSeq with this major development. We will cover the following:
- The new CNV guidelines, the specialized criteria for gains and losses, and how VSClinical simplifies the scoring and interpretation process
- How VS-CNV and VSClinical provides a complete solution for clinical detection and interpretation of CNVs for NGS gene panels and exomes
- The number of CNV specific data sources curated and integrated into the automatic recommendation system
- VSClinical’s integrated Word-based template system for designing custom clinical reports that include quality summary information, coverage at exon and gene level, interpreted variants and CNVs, and patient-level results
We are excited to release this major update to VSClinical, incorporating many small feature enhancements and user requests alongside with the integration of the CNV guidelines. Please join us in this webinar to see how CNVs can be an integrated part of the analysis workflow for your clinical NGS tests.
Annotation capabilities
Darby Kammeraad, a Field Application Scientist at Golden Helix, gives some insight into the advantages of VarSeq's capability with annotations. The number of annotation topics to cover is seemingly limitless. In this webcast, he focuses on key elements that demonstrate the value of Golden Helix's curated annotations available in VarSeq and address some important considerations from our users. We also cover the types and effective utilization of annotations in VarSeq. Finally, he covers how users can create their own annotation sources from the Convert Wizard tool.
AMP-Based Variant Classification with VSClinical
Evaluating somatic variants according to the cancer AMP guidelines can be an extensive process. In addition to the standard collection of all available, clinical evidence for any biomarkers, there is a need to define treatment options following final classification. Even the most adept clinicians familiar to the guidelines suffer from this arduous process and thus need a standardized approach for classifying, interpreting and reporting variants according to the AMP guidelines. VSClinical’s new AMP workflow alleviates these complexities by providing an automated workflow that captures and reports on all critical data present. With the VSClinical AMP workflow, users can also customize clinical reports to reflect your lab’s preferences and branding. This webcast will provide a simple AMP guideline-based demonstration from a user perspective with multiple examples of simple report customizations from the VSClinical interpretation hub.
What you will learn in this webcast:
How VSClinical integrates the tier system to evaluate somatic mutations according to the AMP guidelines, with a focus on SNPs, InDels, CNVs and fusions
Automating the AMP guidelines using Golden Helix CancerKB and lab-specific knowledge databases to streamline variant classifications
Multiple report examples to demonstrate simple Word-based report customization capability
Overall, VSClinical enables labs to test for both germline and somatic variants according to the ACMG and AMP guidelines in an automated fashion and allows users to obtain consistent and accurate results.
VSWarehouse: Tracking Changing Variant Evidence and Classifications
Over the years, VarSeq has evolved into a powerfully efficient next-gen sequencing variant analysis platform. Some of the recent advances Golden Helix has made to this software have been to implement the standard ACMG and AMP guidelines for variant classification and interpretation. The guidelines are composed of many criteria impacting any variant final classification. These criteria consider topics such as frequency of the variant among the population, functional predictions, hotspot pathogenic rich regions in the gene, as well as known clinical submissions from other labs. The reality with this guideline review is that variant evidence can changeover time. Among the long list of databases needed to automate this guideline process, many databases have massive updates or are frequently updated perhaps on a month-to-month basis. So, it follows that any classification can be altered once discoveries for these variants are made. A problem that arises is, how to manage changing classifications, retroactively review previous patient outcomes and updatevariant classifications accordingly. Fortunately, Golden Helix has solved this dilemma with the use of our VSWarehouse genomic repository.
In this webcast, we are going to explore the value and application of VSWarehouse. Our example variants will showcase a situation where variants of uncertain significance ultimately reach a pathogenic classification based on updates to ClinVar. This change will be presented not only in VarSeq with listings of previous samples but also shown directly from the VSWarehouse browser in a ClinVar classification tracker. We will also look at an alternative situation where the classification may change to benign for some previously reported variants which would require follow-up with the patient. The importance of a tool like the ClinVar tracker in VSWarehouse cannot be understated as it is a simple way to comprehensively review the backlog of changing variant classifications when users must update their locked down validated NGS pipeline. Please join us in the upcoming webcast to explore how these features in VarSeq and VSWarehouse work to allow users thorough accountability in updating historical patient results with new variant evidence
Whole Genome Trait Association in SVS
Golden Helix’s SNP & Variation Suite (SVS) has been used by researchers around the world to do trait analysis and association testing on large cohorts of samples in both humans and other species. As Next-Generation Sequencing of whole genomes becomes more affordable, large cohorts of Whole Genome Sequencing (WGS) samples are available to search for additional trait association signals that were not found in array-based testing. In fact, recent papers have shown that WGS analysis using advanced GREML (Genomic Relatedness Restricted Maximum Likelihood) techniques is able to outperform micro-array based GWAS methods in the analysis of complex traits and proportion of the trait heritability explained.
Our latest update release of SVS has expanded the exiting maximum likelihood and GRM methods to support these new techniques. We have also enhanced various other association testing and prediction methodologies. This webcast showcases:
- Newly supported analysis workflow for whole genome variants using LD binning and enhanced GBLUP analysis
- Enhanced gender correction using REML
- Additional capabilities for genomic prediction and phenotype prediction
We are continually improving our products based on our customer’s feedback. We hope you enjoy this recording highlighting the exciting new features and select enhancements we have made.
Reduce Turn-Around with Enhanced Cancer Annotations and CancerKB Updates
Annotation sources are constantly evolving, sometimes quite literally overnight. This is especially true in the case of cancer databases. These ever-evolving annotation sources, coupled with increasing research publications, make it difficult to do variant analysis with up-to-date scientific knowledge. With the resources available to an individual clinician or single lab, this may even prove impossible. Fortunately, VSClinical provides access to the most current clinical annotation sources - automating scoring and interpreting variants according to the most recent ACMP and AMPO guidelines. This includes many fast-changing sources such as ClinVar and COSMIC, as well as expert-curated reviews of literature and the latest drug-labeling from regulatory bodies.
In this webcast, we demonstrate the automation of a cancer workflow with enhanced cancer annotations for somatic and germline cancer variants:
- Golden Helix’s own CancerKB database has been updated to include new interpretations for genes and biomarkers with AMP Tier Level I evidence for drug sensitivity, resistance, diagnostic, and prognostic information.
- We feature a new Golden Helix curated annotation source that automates the scoring of TP53 variants with the special rule specifications by ClinGen’s TP53 Expert Panel.
- The ClinGen Expert Curated Interpretation of Variants has always been available as an annotation source for VarSeq projects, but now the expert comments and interpretations can automatically be pulled into VSClinical and used for clinical reports.
This webcast walks through a hematological-focused cancer workflow that shows off the enhanced cancer annotations and CancerKB updates!
Introducing VSClinical AMP Guidelines: A Comprehensive Workflow for NGS Testi...
The individualized nature of tumors requires genomic testing for providing the best outcomes for patients. Next-Generation 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 that can incorporate all the bioinformatics and clinical evidence involved in following the AMP guidelines for the scoring and reporting of somatic mutations.
Please join us as we reveal the AMP guidelines workflow support in VSClinical. We will cover the entire post-sequencing analytical workflow from FASTQ to clinical report, including:
- Apply the AMP Tiers to the available clinical evidence for Drug Sensitivity, Drug Response, Prognostics and Diagnostics
Support small mutations (SNPs, InDels) along with CNVs, fusions and wild-types as relevant biomarkers for the reporting of clinical evidence
- Develop a lab-specific knowledgebase of interpretations that allow maximum re-use of interpretations and descriptions from one patient to the next
- Leverage the built-in Golden Helix CancerKB interpretation knowledgebase that covers many common genes and biomarkers
- When detecting inherited and not somatic variants in a patient, score and classify them using the ACMG guidelines and report as secondary germline findings
- Use the Oncogenicity scoring system for evaluating the impact of variants in cancer
- Customize your clinical report using Word to reflect your lab's preferences and branding
- Building on the success of VSClinical’s ACMG guidelines, the new VSClinical AMP guidelines enables new and existing labs to provide genetic tests for cancer efficiently and with a focus on delivering consistent and accurate results.
Creating & Managing Reusable Gene Lists with VSClinical
Golden Helix supports performing repeatable clinical workflows designed to meet the needs of your lab's clinical genetic tests. A critical component of any genetic test is the reporting of clinically significant genes and the ability to limit interpretations to a predefined set of test-specific genes. This webinar will cover the upcoming “Managed Gene List” feature of VarSeq and VSClinical which enables the defining and re-use of gene lists outside of individual product templates.
The community has stepped up to provide disease-specific gene lists that are validated and well-researched for specific genetic disorders. In this webinar, we will discuss how these gene lists can be incorporated into your VSClinical workflows and we will demonstrate how these gene lists can be modified to meet the specific needs of your lab.
Things you will learn:
How to manage gene lists in a single location and use them for filtering, annotation, and reporting
How to use the recently released ACMG Secondary Findings v3.0 list for reporting incidental findings
How to leverage the well-researched PanelApp knowledgebase to construct your gene lists based on different levels of evidence for a specific disease
How to define gene lists based on the specific phenotypes and disorders you are targeting with your tests
Exploring New Features and Clinical Reports in the ACMG Guideline Workflow
For the past year, Golden Helix has been preparing a VarSeq release that includes ACMG Guidelines scoring and classification for not only single nucleotide variants but also copy number variants. In the past few months, our webcasts have introduced these guidelines and explored example CNVs that demonstrated the automated scoring of CNVs according to the new ACMG CNV Guidelines. However, there are many other new features and upgrades that have been incorporated into this VarSeq release. These upgrades have largely been driven by input from VarSeq users! That’s why I am very excited to explore these features together in the upcoming webcast “Exploring New Features and Clinical Reports in the ACMG Guideline Workflow”. In this webcast, we will walk through a workflow with SNVs and CNVs highlighting many of the new features and upgrades that will improve and streamline your ACMG workflow. Notably, we will see how these new features can also be incorporated into clinical reports.
Specifically, we will cover the following features:
New and improved ACMG Classifier algorithms
New and improved assessment catalogs for saving classifications and interpretations
New Project Options interface for creating patient evaluations
Now offering three new word-based clinical report templates
Inclusion of additional sections and features to the clinical reports
Enhanced report customization capability
Family-Based Workflows in VarSeq and VSClinical
Golden Helix is a single testing paradigm that allows users to start with next-generation sequencing data and finish with a clinical report. Our solutions are comprehensive as they are all performed in one software suite, which can save time and money as they prevent the need to outsource to different companies. Furthermore, our software is fully transparent in that you have full control over the steps performed in your analysis. Golden Helix is also on the forefront in the clinical workspace as we have implemented the ACMG and AMP guidelines to evaluate single nucleotide variants, insertions and deletions, as well as structural variants.
Beyond these functionalities, Golden Helix provides the ability to perform family-based analysis. Our ACMG and Exome trio templates give users a starting point to understand the different inheritance models ranging from transmitted to de novo variants, but we also have features that can provide additional evidence for both traditional and nontraditional family-based workflows. Specifically, we have algorithms that can be implemented to look at extended pedigree information and sample relatedness as well as options for examining whether a given variant such as a CNV segregates among similarly affected family members. In this webcast, we would like to demonstrate these features and show some solutions for the analysis of different family structures.
As an overview, this webcast will cover:
- Implementing filter logics for different family structures
- Algorithms that can be used for establishing clinical significance in family-based workflows
- Visualization capabilities for further understanding of inheritance models
- Confirming and evaluating transmitted CNVs
VSWarehouse Upgrade: Somatic Variant Analysis via VSClinical AMP Guidelines
Join us as we delve into VSWarehouse with a focus on our new capability of storing somatic variant projects and catalogs built for the AMP Guidelines within VSClinical.
We will also be demonstrating how VSWarehouse efficiently navigates through stored variants via the VSWarehouse Browser.
We hope you enjoy as we explore and leverage a comprehensive set of genomic data stored within VSWarehouse to ensure rapid workflow efficiency.
In this webcast, you will learn:
How to access the VSWarehouse terminal within VarSeq
Leverage the VSWarehouse genomic database in a VarSeq workflow
Explore the stored genomic data via the VSWarehouse Browser
You can read more about what this webcast covers over on our blog: https://blog.goldenhelix.com/vswarehouse-upgrade-somatic-variant-analysis-via-vsclinical-amp-guidelines/
PhoRank 2.0: Improved Phenotype-Based Gene Ranking in VarSeq
When performing variant analysis on whole exome or large gene panels, clinicians must sort through thousands of variants to determine which variants are most likely to be associated with the patient’s phenotypes. To assist with this process, we have implemented the PhoRank algorithm, which incorporates phenotypic associations to highlight the most relevant genes with potentially damaging variants. PhoRank 1.0 supports researchers leveraging all possible gene-disease associations by traversing multiple gene and pathway ontologies. Recent papers have demonstrated new techniques that have improved ranking performance in a clinical context. We have incorporated these new strategies into PhoRank 2.0: providing better ranking and improved computational performance for most clinically diagnostic and testing scenarios. Join us in this webinar as we cover:
Utility of gene ranking in genetic testing
Scenarios that warrant the use of PhoRank 2.0
New ranking strategies provided by recent papers
Benchmarks of PhoRank 2.0 on published datasets
Golden Helix provides a comprehensive solution for NGS testing labs to perform best practice guidelines such as ACMG and AMP. Our gene ranking methods provide a vital role in scaling tests to large gene panels and exomes. Please join us as we review the testing workflow and how this significant update to our gene ranking algorithm fits into the testing workflow.
Advanced Report Customization via VSClinical
Webcast 12.8.21 Advanced Report Customization via VSClinical
Automating the ACMG Guidelines with VSClinical
Clinical Genetic testing requires a complex analysis using the totality of our knowledge about the clinical relevance of a variant and a gene. This includes bioinformatic evidence as well as clinical evidence. The ACMG Guidelines provided a framework in which to score variants based on this evidence, and while some of those scoring criteria require close consultation of the clinical context for a given patient, much of it can be automated.
In this webcast, we review how VSClinical automates the ACMG scoring guidelines while integrating the collective lab expertise from previously classified variants and preferences about genes. We will cover:
Using the ACMG Auto Classifier as part the filtering strategy for gene panels and trio workflows
How gene preferences such as the default transcript, inheritance model, and disorder are updated and saved from VSClinical and used in all future analysis
How the per-variant recommendation engine builds on the auto-classification with descriptive reasons for answering each criterion yes or no
Using the auto-interpretation to present the evidence for all scored criteria in a human-readable paragraph
Working with VSClinical’s self-learning knowledgebase that incorporates previously classified variants and genes inform the interpretation of new variants!
The ClinGen Sequence Variant Interpretation Working Group: Refining Criteria ...
The ClinGen Sequence Variant Interpretation Working Group: Refining Criteria ...Human Variome Project
A key barrier to the efficient clinical utilization of genome sequence data is the lack of a systematic approach for interpreting the pathogenicity of genetic variants, with resultant discordance among laboratories and researchers in classification. The ClinGen (Clinical Genome) Project has been funded by the United States National Institutes of Health with a goal of maximizing the clinical relevance of results from genetic testing. ClinGen has established a Sequence Variant Interpretation (SVI) Working Group to refine and standardize the approach to pathogenicity classification. Recently the American College of Medical Genetics and Genomics (ACMG) published guidelines [1] that emerged from a workgroup that represented the expert opinion of clinical laboratory directors and genetics clinicians. These guidelines were developed to help clinical laboratories that report results from sequencing of single genes, panels, exomes, and genomes. The ClinGen SVI has set short term and long term objectives for advancing the field of pathogenicity interpretation using the ACMG framework as a starting point. There is consensus within the field that correct classification of variants requires integrating multiple lines of evidence, including, clinico-pathologic, epidemiologic, bioinformatics (in silico), and in vitro data. How best to combine them is unclear. The ACMG framework described different categories of evidence and assigned preliminary assessments of what comprises weak or strong evidence favoring a variant’s pathogenicity or neutrality and preliminary rule- based algorithms of how to combine evidence. In the short term, the ClinGen SVI has set up sub-committees to apply more precision in defining criteria for pathogenicity and what comprises strong and weak evidence. In the long term, the ClinGen SVI looks to transition from qualitative descriptions to a quantitative system that can assign an empirically derived probability of pathogenicity for each variant. Preliminary analyses suggest that there will be general rules that apply to all genes, as well as specific approaches for different genetic disorders. Well characterized databases of variants for each genetic disorder will be critical to the process. Funded by the National Human Genome Research Institute through the following three grants: U41 HG006834-01A1, U01 HG007437- 01, U01 HG007436-01, and by the National Cancer Institute through contract HHSN261200800001E. Reference: 1. Richards S, Aziz N, Bale S, et al. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine2015;17(5):405-424.Rare diseases in children and genetic diagnosis - part 1 [Today's paper]
Today's paper is a review for genetic diagnosis of paediatric rare diseases.
The title is "Paediatric genomics: diagnosing rare disease in children." published in 2018, Nature review genetics.
Thanks for watching!
doi: 10.1038/nrg.2017.116.
Cancer Diagnostics Laboratory | NeoGenomics | April 2014 | Company Overview P...
Cancer Diagnostics Laboratory | NeoGenomics | April 2014 | Company Overview P...NeoGenomics Laboratory | Cancer Diagnostics
Cancer Diagnostics Reference Laboratory / NeoGenomics April 2014 investors company overview presentation. This presentation highlights the following:
--Fast growing cancer genetics lab servicing Oncologists, Pathologists and Hostpitals
--Strategic client partnerships created by "Tech-Only" model
--Dynamic, rapidly-growing and consolidating industry
Industry-leading revenue & test volume growth
--Strong productivity and operating leverage leading to accelerating cash flow and net income
--Strong Management Team with large cap lab experienceProcessing Hereditary Cancer Panels in VarSeq
Processing variants related to cancer is an incredibly critical process and a primary goal is to not only assess the variants rapidly but also accurately. A major improvement to cancer panel workflow efficiency is to utilize VarSeq for variant filtering, annotating, and interpretation. In this webcast we’ll cover some important quality assurance capabilities VarSeq provides, multiple approaches to build targeted panels, how to access/utilize numerous cancer annotations, and finally work through the ACMG guideline process on the selected germline cancer variants. The overall goal is to cover the basics of building the cancer gene panel project template so that it can be used routinely in high throughput environments.
Using Golden Helix CancerKB to Accelerate NGS Cancer Testing
Next Generation Sequencing is being rapidly integrated into the oncology field. From the clinical perspective, both somatic and germline NGS results are informative for hereditary cancer risk and treatment strategies. There are numerous scattered resources that inform the clinical significance of a somatic mutation for a patient’s tumor type. Similarly, there are many FDA-approved anti-cancer agents and drugs with changing indications, and opportunities for off-label use. Even more, there are clinical trials all over the world that though they require specific genetic alterations for enrollment eligibility, they could provide more treatment options for cancer patients.
What’s the bottom line? It is certainly a huge undertaking to evaluate a gene or biomarker’s role in cancer or clinical significance. It requires sifting through trials that are relevant for the patient from the abundance of literature available, not to mention staying well-informed on new research as it is published.
Golden Helix CancerKB offers a solution. We demonstrate the application of CancerKB and how easy somatic variant analysis can be in VSClinical. Namely, I will deep dive into the following topics:
The process our expert curators use to produce high-quality cancer interpretations
Examples of complex biomarker interpretations simplified using CancerKB
Report content filled in by CancerKB, even for rare genes
Integrating customer feedback and the future of CancerKB
ACMG-Based Variant Classification with VSClinical
Evaluating variants according to the ACMG guidelines can be an extensive process as it requires an in-depth understanding of all available criteria for any variant. Even the most adept clinicians familiar to the guidelines suffer from this tedious manual process and from the challenge of teaching these fundamentals to new technicians. VSClinical is an automated solution to the complex ACMG guidelines process. In this webcast, we will present how VSClinical follows the true-to-form ACMG classification rules. Additionally, users will discover the value of automating the ACMG guidelines to make variant classification consistent and simplify the interpretation process for those less familiar with ACMG criteria.
Introducing Drugs & Trials for Cancer Diagnostics
When interpreting a variant using the AMP/ASCO guidelines for somatic variant interpretation, clinicians must determine whether the variant can be considered a biomarker that affects clinical care by predicting sensitivity, resistance, or toxicity to a specific therapy. Such a determination requires the investigation of multiple evidence sources, including clinical trials, FDA approved therapies and peer-reviewed studies. Unfortunately, strong evidence linking specific genetic biomarkers to FDA-approved therapies only exists for a small number of cancers. Thus, most variants require an exploration of clinical practice guidelines, peer-reviewed literature, and large-scale cancer mutation databases to effectively assess the clinical significance of a given mutation.
This webcast explores this new incorporation of Drugs & Trials Annotations in VSClinical's AMP Workflow covering:
Identification of relevant clinical evidence for drug sensitivity and resistance based on patient biomarkers and tumor type
Review of clinical trial information including inclusion criteria, trial status, and contact information
Management of citations associated with relevant, targeted therapies
Evaluation of a biomarkers clinical evidence tier based on available evidence for drug sensitivity and resistance
Introducing Drugs & Trials for Cancer Diagnostics
When interpreting a variant using the AMP/ASCO guidelines for somatic variant interpretation, clinicians must determine whether the variant can be considered a biomarker that affects clinical care by predicting sensitivity, resistance, or toxicity to a specific therapy. Such a determination requires the investigation of multiple evidence sources, including clinical trials, FDA approved therapies and peer-reviewed studies. Unfortunately, strong evidence linking specific genetic biomarkers to FDA-approved therapies only exists for a small number of cancers. Thus, most variants require an exploration of clinical practice guidelines, peer-reviewed literature, and large-scale cancer mutation databases to effectively assess the clinical significance of a given mutation.
This webcast explores this new incorporation of Drugs & Trials Annotations in VSClinical's AMP Workflow covering:
Identification of relevant clinical evidence for drug sensitivity and resistance based on patient biomarkers and tumor type
Review of clinical trial information including inclusion criteria, trial status, and contact information
Management of citations associated with relevant, targeted therapies
Evaluation of a biomarkers clinical evidence tier based on available evidence for drug sensitivity and resistance
More Related Content
What's hot
Annotation capabilities
Darby Kammeraad, a Field Application Scientist at Golden Helix, gives some insight into the advantages of VarSeq's capability with annotations. The number of annotation topics to cover is seemingly limitless. In this webcast, he focuses on key elements that demonstrate the value of Golden Helix's curated annotations available in VarSeq and address some important considerations from our users. We also cover the types and effective utilization of annotations in VarSeq. Finally, he covers how users can create their own annotation sources from the Convert Wizard tool.
AMP-Based Variant Classification with VSClinical
Evaluating somatic variants according to the cancer AMP guidelines can be an extensive process. In addition to the standard collection of all available, clinical evidence for any biomarkers, there is a need to define treatment options following final classification. Even the most adept clinicians familiar to the guidelines suffer from this arduous process and thus need a standardized approach for classifying, interpreting and reporting variants according to the AMP guidelines. VSClinical’s new AMP workflow alleviates these complexities by providing an automated workflow that captures and reports on all critical data present. With the VSClinical AMP workflow, users can also customize clinical reports to reflect your lab’s preferences and branding. This webcast will provide a simple AMP guideline-based demonstration from a user perspective with multiple examples of simple report customizations from the VSClinical interpretation hub.
What you will learn in this webcast:
How VSClinical integrates the tier system to evaluate somatic mutations according to the AMP guidelines, with a focus on SNPs, InDels, CNVs and fusions
Automating the AMP guidelines using Golden Helix CancerKB and lab-specific knowledge databases to streamline variant classifications
Multiple report examples to demonstrate simple Word-based report customization capability
Overall, VSClinical enables labs to test for both germline and somatic variants according to the ACMG and AMP guidelines in an automated fashion and allows users to obtain consistent and accurate results.
VSWarehouse: Tracking Changing Variant Evidence and Classifications
Over the years, VarSeq has evolved into a powerfully efficient next-gen sequencing variant analysis platform. Some of the recent advances Golden Helix has made to this software have been to implement the standard ACMG and AMP guidelines for variant classification and interpretation. The guidelines are composed of many criteria impacting any variant final classification. These criteria consider topics such as frequency of the variant among the population, functional predictions, hotspot pathogenic rich regions in the gene, as well as known clinical submissions from other labs. The reality with this guideline review is that variant evidence can changeover time. Among the long list of databases needed to automate this guideline process, many databases have massive updates or are frequently updated perhaps on a month-to-month basis. So, it follows that any classification can be altered once discoveries for these variants are made. A problem that arises is, how to manage changing classifications, retroactively review previous patient outcomes and updatevariant classifications accordingly. Fortunately, Golden Helix has solved this dilemma with the use of our VSWarehouse genomic repository.
In this webcast, we are going to explore the value and application of VSWarehouse. Our example variants will showcase a situation where variants of uncertain significance ultimately reach a pathogenic classification based on updates to ClinVar. This change will be presented not only in VarSeq with listings of previous samples but also shown directly from the VSWarehouse browser in a ClinVar classification tracker. We will also look at an alternative situation where the classification may change to benign for some previously reported variants which would require follow-up with the patient. The importance of a tool like the ClinVar tracker in VSWarehouse cannot be understated as it is a simple way to comprehensively review the backlog of changing variant classifications when users must update their locked down validated NGS pipeline. Please join us in the upcoming webcast to explore how these features in VarSeq and VSWarehouse work to allow users thorough accountability in updating historical patient results with new variant evidence
Whole Genome Trait Association in SVS
Golden Helix’s SNP & Variation Suite (SVS) has been used by researchers around the world to do trait analysis and association testing on large cohorts of samples in both humans and other species. As Next-Generation Sequencing of whole genomes becomes more affordable, large cohorts of Whole Genome Sequencing (WGS) samples are available to search for additional trait association signals that were not found in array-based testing. In fact, recent papers have shown that WGS analysis using advanced GREML (Genomic Relatedness Restricted Maximum Likelihood) techniques is able to outperform micro-array based GWAS methods in the analysis of complex traits and proportion of the trait heritability explained.
Our latest update release of SVS has expanded the exiting maximum likelihood and GRM methods to support these new techniques. We have also enhanced various other association testing and prediction methodologies. This webcast showcases:
- Newly supported analysis workflow for whole genome variants using LD binning and enhanced GBLUP analysis
- Enhanced gender correction using REML
- Additional capabilities for genomic prediction and phenotype prediction
We are continually improving our products based on our customer’s feedback. We hope you enjoy this recording highlighting the exciting new features and select enhancements we have made.
Reduce Turn-Around with Enhanced Cancer Annotations and CancerKB Updates
Annotation sources are constantly evolving, sometimes quite literally overnight. This is especially true in the case of cancer databases. These ever-evolving annotation sources, coupled with increasing research publications, make it difficult to do variant analysis with up-to-date scientific knowledge. With the resources available to an individual clinician or single lab, this may even prove impossible. Fortunately, VSClinical provides access to the most current clinical annotation sources - automating scoring and interpreting variants according to the most recent ACMP and AMPO guidelines. This includes many fast-changing sources such as ClinVar and COSMIC, as well as expert-curated reviews of literature and the latest drug-labeling from regulatory bodies.
In this webcast, we demonstrate the automation of a cancer workflow with enhanced cancer annotations for somatic and germline cancer variants:
- Golden Helix’s own CancerKB database has been updated to include new interpretations for genes and biomarkers with AMP Tier Level I evidence for drug sensitivity, resistance, diagnostic, and prognostic information.
- We feature a new Golden Helix curated annotation source that automates the scoring of TP53 variants with the special rule specifications by ClinGen’s TP53 Expert Panel.
- The ClinGen Expert Curated Interpretation of Variants has always been available as an annotation source for VarSeq projects, but now the expert comments and interpretations can automatically be pulled into VSClinical and used for clinical reports.
This webcast walks through a hematological-focused cancer workflow that shows off the enhanced cancer annotations and CancerKB updates!
Introducing VSClinical AMP Guidelines: A Comprehensive Workflow for NGS Testi...
The individualized nature of tumors requires genomic testing for providing the best outcomes for patients. Next-Generation 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 that can incorporate all the bioinformatics and clinical evidence involved in following the AMP guidelines for the scoring and reporting of somatic mutations.
Please join us as we reveal the AMP guidelines workflow support in VSClinical. We will cover the entire post-sequencing analytical workflow from FASTQ to clinical report, including:
- Apply the AMP Tiers to the available clinical evidence for Drug Sensitivity, Drug Response, Prognostics and Diagnostics
Support small mutations (SNPs, InDels) along with CNVs, fusions and wild-types as relevant biomarkers for the reporting of clinical evidence
- Develop a lab-specific knowledgebase of interpretations that allow maximum re-use of interpretations and descriptions from one patient to the next
- Leverage the built-in Golden Helix CancerKB interpretation knowledgebase that covers many common genes and biomarkers
- When detecting inherited and not somatic variants in a patient, score and classify them using the ACMG guidelines and report as secondary germline findings
- Use the Oncogenicity scoring system for evaluating the impact of variants in cancer
- Customize your clinical report using Word to reflect your lab's preferences and branding
- Building on the success of VSClinical’s ACMG guidelines, the new VSClinical AMP guidelines enables new and existing labs to provide genetic tests for cancer efficiently and with a focus on delivering consistent and accurate results.
Creating & Managing Reusable Gene Lists with VSClinical
Golden Helix supports performing repeatable clinical workflows designed to meet the needs of your lab's clinical genetic tests. A critical component of any genetic test is the reporting of clinically significant genes and the ability to limit interpretations to a predefined set of test-specific genes. This webinar will cover the upcoming “Managed Gene List” feature of VarSeq and VSClinical which enables the defining and re-use of gene lists outside of individual product templates.
The community has stepped up to provide disease-specific gene lists that are validated and well-researched for specific genetic disorders. In this webinar, we will discuss how these gene lists can be incorporated into your VSClinical workflows and we will demonstrate how these gene lists can be modified to meet the specific needs of your lab.
Things you will learn:
How to manage gene lists in a single location and use them for filtering, annotation, and reporting
How to use the recently released ACMG Secondary Findings v3.0 list for reporting incidental findings
How to leverage the well-researched PanelApp knowledgebase to construct your gene lists based on different levels of evidence for a specific disease
How to define gene lists based on the specific phenotypes and disorders you are targeting with your tests
Exploring New Features and Clinical Reports in the ACMG Guideline Workflow
For the past year, Golden Helix has been preparing a VarSeq release that includes ACMG Guidelines scoring and classification for not only single nucleotide variants but also copy number variants. In the past few months, our webcasts have introduced these guidelines and explored example CNVs that demonstrated the automated scoring of CNVs according to the new ACMG CNV Guidelines. However, there are many other new features and upgrades that have been incorporated into this VarSeq release. These upgrades have largely been driven by input from VarSeq users! That’s why I am very excited to explore these features together in the upcoming webcast “Exploring New Features and Clinical Reports in the ACMG Guideline Workflow”. In this webcast, we will walk through a workflow with SNVs and CNVs highlighting many of the new features and upgrades that will improve and streamline your ACMG workflow. Notably, we will see how these new features can also be incorporated into clinical reports.
Specifically, we will cover the following features:
New and improved ACMG Classifier algorithms
New and improved assessment catalogs for saving classifications and interpretations
New Project Options interface for creating patient evaluations
Now offering three new word-based clinical report templates
Inclusion of additional sections and features to the clinical reports
Enhanced report customization capability
Family-Based Workflows in VarSeq and VSClinical
Golden Helix is a single testing paradigm that allows users to start with next-generation sequencing data and finish with a clinical report. Our solutions are comprehensive as they are all performed in one software suite, which can save time and money as they prevent the need to outsource to different companies. Furthermore, our software is fully transparent in that you have full control over the steps performed in your analysis. Golden Helix is also on the forefront in the clinical workspace as we have implemented the ACMG and AMP guidelines to evaluate single nucleotide variants, insertions and deletions, as well as structural variants.
Beyond these functionalities, Golden Helix provides the ability to perform family-based analysis. Our ACMG and Exome trio templates give users a starting point to understand the different inheritance models ranging from transmitted to de novo variants, but we also have features that can provide additional evidence for both traditional and nontraditional family-based workflows. Specifically, we have algorithms that can be implemented to look at extended pedigree information and sample relatedness as well as options for examining whether a given variant such as a CNV segregates among similarly affected family members. In this webcast, we would like to demonstrate these features and show some solutions for the analysis of different family structures.
As an overview, this webcast will cover:
- Implementing filter logics for different family structures
- Algorithms that can be used for establishing clinical significance in family-based workflows
- Visualization capabilities for further understanding of inheritance models
- Confirming and evaluating transmitted CNVs
VSWarehouse Upgrade: Somatic Variant Analysis via VSClinical AMP Guidelines
Join us as we delve into VSWarehouse with a focus on our new capability of storing somatic variant projects and catalogs built for the AMP Guidelines within VSClinical.
We will also be demonstrating how VSWarehouse efficiently navigates through stored variants via the VSWarehouse Browser.
We hope you enjoy as we explore and leverage a comprehensive set of genomic data stored within VSWarehouse to ensure rapid workflow efficiency.
In this webcast, you will learn:
How to access the VSWarehouse terminal within VarSeq
Leverage the VSWarehouse genomic database in a VarSeq workflow
Explore the stored genomic data via the VSWarehouse Browser
You can read more about what this webcast covers over on our blog: https://blog.goldenhelix.com/vswarehouse-upgrade-somatic-variant-analysis-via-vsclinical-amp-guidelines/
PhoRank 2.0: Improved Phenotype-Based Gene Ranking in VarSeq
When performing variant analysis on whole exome or large gene panels, clinicians must sort through thousands of variants to determine which variants are most likely to be associated with the patient’s phenotypes. To assist with this process, we have implemented the PhoRank algorithm, which incorporates phenotypic associations to highlight the most relevant genes with potentially damaging variants. PhoRank 1.0 supports researchers leveraging all possible gene-disease associations by traversing multiple gene and pathway ontologies. Recent papers have demonstrated new techniques that have improved ranking performance in a clinical context. We have incorporated these new strategies into PhoRank 2.0: providing better ranking and improved computational performance for most clinically diagnostic and testing scenarios. Join us in this webinar as we cover:
Utility of gene ranking in genetic testing
Scenarios that warrant the use of PhoRank 2.0
New ranking strategies provided by recent papers
Benchmarks of PhoRank 2.0 on published datasets
Golden Helix provides a comprehensive solution for NGS testing labs to perform best practice guidelines such as ACMG and AMP. Our gene ranking methods provide a vital role in scaling tests to large gene panels and exomes. Please join us as we review the testing workflow and how this significant update to our gene ranking algorithm fits into the testing workflow.
Advanced Report Customization via VSClinical
Webcast 12.8.21 Advanced Report Customization via VSClinical
Automating the ACMG Guidelines with VSClinical
Clinical Genetic testing requires a complex analysis using the totality of our knowledge about the clinical relevance of a variant and a gene. This includes bioinformatic evidence as well as clinical evidence. The ACMG Guidelines provided a framework in which to score variants based on this evidence, and while some of those scoring criteria require close consultation of the clinical context for a given patient, much of it can be automated.
In this webcast, we review how VSClinical automates the ACMG scoring guidelines while integrating the collective lab expertise from previously classified variants and preferences about genes. We will cover:
Using the ACMG Auto Classifier as part the filtering strategy for gene panels and trio workflows
How gene preferences such as the default transcript, inheritance model, and disorder are updated and saved from VSClinical and used in all future analysis
How the per-variant recommendation engine builds on the auto-classification with descriptive reasons for answering each criterion yes or no
Using the auto-interpretation to present the evidence for all scored criteria in a human-readable paragraph
Working with VSClinical’s self-learning knowledgebase that incorporates previously classified variants and genes inform the interpretation of new variants!
The ClinGen Sequence Variant Interpretation Working Group: Refining Criteria ...
The ClinGen Sequence Variant Interpretation Working Group: Refining Criteria ...Human Variome Project
A key barrier to the efficient clinical utilization of genome sequence data is the lack of a systematic approach for interpreting the pathogenicity of genetic variants, with resultant discordance among laboratories and researchers in classification. The ClinGen (Clinical Genome) Project has been funded by the United States National Institutes of Health with a goal of maximizing the clinical relevance of results from genetic testing. ClinGen has established a Sequence Variant Interpretation (SVI) Working Group to refine and standardize the approach to pathogenicity classification. Recently the American College of Medical Genetics and Genomics (ACMG) published guidelines [1] that emerged from a workgroup that represented the expert opinion of clinical laboratory directors and genetics clinicians. These guidelines were developed to help clinical laboratories that report results from sequencing of single genes, panels, exomes, and genomes. The ClinGen SVI has set short term and long term objectives for advancing the field of pathogenicity interpretation using the ACMG framework as a starting point. There is consensus within the field that correct classification of variants requires integrating multiple lines of evidence, including, clinico-pathologic, epidemiologic, bioinformatics (in silico), and in vitro data. How best to combine them is unclear. The ACMG framework described different categories of evidence and assigned preliminary assessments of what comprises weak or strong evidence favoring a variant’s pathogenicity or neutrality and preliminary rule- based algorithms of how to combine evidence. In the short term, the ClinGen SVI has set up sub-committees to apply more precision in defining criteria for pathogenicity and what comprises strong and weak evidence. In the long term, the ClinGen SVI looks to transition from qualitative descriptions to a quantitative system that can assign an empirically derived probability of pathogenicity for each variant. Preliminary analyses suggest that there will be general rules that apply to all genes, as well as specific approaches for different genetic disorders. Well characterized databases of variants for each genetic disorder will be critical to the process. Funded by the National Human Genome Research Institute through the following three grants: U41 HG006834-01A1, U01 HG007437- 01, U01 HG007436-01, and by the National Cancer Institute through contract HHSN261200800001E. Reference: 1. Richards S, Aziz N, Bale S, et al. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine2015;17(5):405-424.Rare diseases in children and genetic diagnosis - part 1 [Today's paper]
Today's paper is a review for genetic diagnosis of paediatric rare diseases.
The title is "Paediatric genomics: diagnosing rare disease in children." published in 2018, Nature review genetics.
Thanks for watching!
doi: 10.1038/nrg.2017.116.
Cancer Diagnostics Laboratory | NeoGenomics | April 2014 | Company Overview P...
Cancer Diagnostics Laboratory | NeoGenomics | April 2014 | Company Overview P...NeoGenomics Laboratory | Cancer Diagnostics
Cancer Diagnostics Reference Laboratory / NeoGenomics April 2014 investors company overview presentation. This presentation highlights the following:
--Fast growing cancer genetics lab servicing Oncologists, Pathologists and Hostpitals
--Strategic client partnerships created by "Tech-Only" model
--Dynamic, rapidly-growing and consolidating industry
Industry-leading revenue & test volume growth
--Strong productivity and operating leverage leading to accelerating cash flow and net income
--Strong Management Team with large cap lab experienceProcessing Hereditary Cancer Panels in VarSeq
Processing variants related to cancer is an incredibly critical process and a primary goal is to not only assess the variants rapidly but also accurately. A major improvement to cancer panel workflow efficiency is to utilize VarSeq for variant filtering, annotating, and interpretation. In this webcast we’ll cover some important quality assurance capabilities VarSeq provides, multiple approaches to build targeted panels, how to access/utilize numerous cancer annotations, and finally work through the ACMG guideline process on the selected germline cancer variants. The overall goal is to cover the basics of building the cancer gene panel project template so that it can be used routinely in high throughput environments.
Using Golden Helix CancerKB to Accelerate NGS Cancer Testing
Next Generation Sequencing is being rapidly integrated into the oncology field. From the clinical perspective, both somatic and germline NGS results are informative for hereditary cancer risk and treatment strategies. There are numerous scattered resources that inform the clinical significance of a somatic mutation for a patient’s tumor type. Similarly, there are many FDA-approved anti-cancer agents and drugs with changing indications, and opportunities for off-label use. Even more, there are clinical trials all over the world that though they require specific genetic alterations for enrollment eligibility, they could provide more treatment options for cancer patients.
What’s the bottom line? It is certainly a huge undertaking to evaluate a gene or biomarker’s role in cancer or clinical significance. It requires sifting through trials that are relevant for the patient from the abundance of literature available, not to mention staying well-informed on new research as it is published.
Golden Helix CancerKB offers a solution. We demonstrate the application of CancerKB and how easy somatic variant analysis can be in VSClinical. Namely, I will deep dive into the following topics:
The process our expert curators use to produce high-quality cancer interpretations
Examples of complex biomarker interpretations simplified using CancerKB
Report content filled in by CancerKB, even for rare genes
Integrating customer feedback and the future of CancerKB
ACMG-Based Variant Classification with VSClinical
Evaluating variants according to the ACMG guidelines can be an extensive process as it requires an in-depth understanding of all available criteria for any variant. Even the most adept clinicians familiar to the guidelines suffer from this tedious manual process and from the challenge of teaching these fundamentals to new technicians. VSClinical is an automated solution to the complex ACMG guidelines process. In this webcast, we will present how VSClinical follows the true-to-form ACMG classification rules. Additionally, users will discover the value of automating the ACMG guidelines to make variant classification consistent and simplify the interpretation process for those less familiar with ACMG criteria.
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VSWarehouse: Tracking Changing Variant Evidence and Classifications
VSWarehouse: Tracking Changing Variant Evidence and Classifications
Reduce Turn-Around with Enhanced Cancer Annotations and CancerKB Updates
Reduce Turn-Around with Enhanced Cancer Annotations and CancerKB Updates
Introducing VSClinical AMP Guidelines: A Comprehensive Workflow for NGS Testi...
Introducing VSClinical AMP Guidelines: A Comprehensive Workflow for NGS Testi...
Creating & Managing Reusable Gene Lists with VSClinical
Creating & Managing Reusable Gene Lists with VSClinical
Exploring New Features and Clinical Reports in the ACMG Guideline Workflow
Exploring New Features and Clinical Reports in the ACMG Guideline Workflow
VSWarehouse Upgrade: Somatic Variant Analysis via VSClinical AMP Guidelines
VSWarehouse Upgrade: Somatic Variant Analysis via VSClinical AMP Guidelines
PhoRank 2.0: Improved Phenotype-Based Gene Ranking in VarSeq
PhoRank 2.0: Improved Phenotype-Based Gene Ranking in VarSeq
The ClinGen Sequence Variant Interpretation Working Group: Refining Criteria ...
The ClinGen Sequence Variant Interpretation Working Group: Refining Criteria ...
Rare diseases in children and genetic diagnosis - part 1 [Today's paper]
Rare diseases in children and genetic diagnosis - part 1 [Today's paper]
Cancer Diagnostics Laboratory | NeoGenomics | April 2014 | Company Overview P...
Cancer Diagnostics Laboratory | NeoGenomics | April 2014 | Company Overview P...
Using Golden Helix CancerKB to Accelerate NGS Cancer Testing
Using Golden Helix CancerKB to Accelerate NGS Cancer Testing
Similar to Clinical Validation of Copy Number Variants Using the AMP Guidelines
Introducing Drugs & Trials for Cancer Diagnostics
When interpreting a variant using the AMP/ASCO guidelines for somatic variant interpretation, clinicians must determine whether the variant can be considered a biomarker that affects clinical care by predicting sensitivity, resistance, or toxicity to a specific therapy. Such a determination requires the investigation of multiple evidence sources, including clinical trials, FDA approved therapies and peer-reviewed studies. Unfortunately, strong evidence linking specific genetic biomarkers to FDA-approved therapies only exists for a small number of cancers. Thus, most variants require an exploration of clinical practice guidelines, peer-reviewed literature, and large-scale cancer mutation databases to effectively assess the clinical significance of a given mutation.
This webcast explores this new incorporation of Drugs & Trials Annotations in VSClinical's AMP Workflow covering:
Identification of relevant clinical evidence for drug sensitivity and resistance based on patient biomarkers and tumor type
Review of clinical trial information including inclusion criteria, trial status, and contact information
Management of citations associated with relevant, targeted therapies
Evaluation of a biomarkers clinical evidence tier based on available evidence for drug sensitivity and resistance
Introducing Drugs & Trials for Cancer Diagnostics
When interpreting a variant using the AMP/ASCO guidelines for somatic variant interpretation, clinicians must determine whether the variant can be considered a biomarker that affects clinical care by predicting sensitivity, resistance, or toxicity to a specific therapy. Such a determination requires the investigation of multiple evidence sources, including clinical trials, FDA approved therapies and peer-reviewed studies. Unfortunately, strong evidence linking specific genetic biomarkers to FDA-approved therapies only exists for a small number of cancers. Thus, most variants require an exploration of clinical practice guidelines, peer-reviewed literature, and large-scale cancer mutation databases to effectively assess the clinical significance of a given mutation.
This webcast explores this new incorporation of Drugs & Trials Annotations in VSClinical's AMP Workflow covering:
Identification of relevant clinical evidence for drug sensitivity and resistance based on patient biomarkers and tumor type
Review of clinical trial information including inclusion criteria, trial status, and contact information
Management of citations associated with relevant, targeted therapies
Evaluation of a biomarkers clinical evidence tier based on available evidence for drug sensitivity and resistance
Efficiently Following the AMP Guidelines with VSClinical and Golden Helix Can...
Interpreting somatic variants for the clinical genetic testing of tumors requires hands-on time of the most skilled clinical lab personnel. Various clinical and genomic sources must be queried, papers and guidelines referenced, and an evaluation of the clinical actionability of the mutation determined by the following the AMP guidelines. Yet, there is tremendous potential for reuse of this time consuming and valuable work!
Earlier this summer we launched our VSClinical AMP Guidelines workflow which integrates a lab-specific knowledgebase that saves every biomarkers interpretation in up to seven different snippets that ar reusable across various genomic and clinical contexts. Furthermore, our cancer workflow is bundled with the Golden Helix CancerKB, our expert-curated interpretations of the most common biomarkers for the most common cancer types, reducing the time to your first precision medicine report.
Follow along as we cover:
The interpretation of clinically actionable biomarkers for targeted molecular therapy and diagnostic/prognostic clinical reports for cancer
The different levels and scopes of re-use of the interpretation for each biomarker
Saving, re-using and updating these interpretations over time by multiple users within a clinical lab with an integrated lab-specific knowledgebase
The built in Golden Helix CancerKB that provides default interpretations for most cancer genes, biomarkers and many clinically actionable Tier I/II drug sensitivity and resistance interpretations.
In the world of genomics shaping precision medicine in oncology, the limiting factor is the time-to-sign-off on fully interpreted molecular profile reports.
VarSeq 2.3.0: New TSO-500 and Genomic Signature Support in VSClinical AMP
Precision medicine for cancer is rapidly accelerating because of the development and approval of targeted molecular therapies. These therapies require new genomic biomarkers as an indication for use, and require evaluating additional mutation types that are available in comprehensive genomic profiling assays as well as the small variants detected by Next-Generation Sequencing gene panels.
We are excited to announce VarSeq 2.3.0 which will update the VSClinical AMP workflow to meet the growing needs of labs conducting comprehensive genomic profiling (CGP) of tumors. This includes built-in support for the Illumina TruSight Oncology 500 (TSO-500) kit as well as similar kits from other vendors. The VSClinical AMP workflow has also gained native support for the bioinformatic outputs of CGP kits. Join us to learn about comprehensive genomic profiling in cancer, specifically:
Evaluation and clinical reporting of genomic signatures such as Microsatellite (MSI), Tumor mutation burden (TMB), PD-L1, Homologous recombination deficiency (HRD) statuses, and more.
Built-in TSO-500 import and expandable import capabilities for new genomic data types through the new advanced workflow scripting system.
Golden Helix CancerKB updates with report-ready genomic-signature interpretations written for approved therapies as well as gene interpretations for all 500 genes of the TSO-500 panel. In addition, CancerKB scopes have been extended to reference multiple relevant biomarkers in a single interpretation, capture approved therapies at the tumor type level, and include interpretations for clinically relevant negative findings.
Expanded clinical trial support to include international trials and the ability to search within proximity of European postal codes. VSClinical is accessing all active studies in AACT/ClinicalTrials.gov wherein users can search and select trials based on relevant drugs, biomarkers, and the geographic distance to the patient or testing site.
VarSeq 2.3.0 will deliver powerful capabilities for genomic profiling in cancer, enabling a new level of personalized and effective care for your patients. We look forward to demonstrating these updates and Golden Helix’s continued innovation making the VarSeq Clinical Suite the NGS analysis platform of choice for germline and cancer testing.
VarSeq 2.5.0: VSClinical AMP Workflow from the User Perspective
With our recent launch of VarSeq 2.5.0, our ability to expedite somatic analysis for NGS labs is more accessible than ever before. Our recent webcasts have shown our range of updates, including our new oncogenicity classifier and carrier status workflows:
Identifying Oncogenic Variants in VarSeq
VarSeq 2.5.0: Empowering Family Planning through Carrier Screening Analysis
In this user perspective webcast, we will highlight how the combination of our new oncogenicity classifier and the updates to our CancerKB database streamline the interpretation of oncogenic variants. In addition, as NGS labs progress from gene panels to WES analysis for ideal genomic signature generation, we will demonstrate how a VarSeq somatic workflow can scale with these increased scopes of data analysis with ease.
Our user perspective webcast will cover:
Application of virtual panels to WES tumor/normal workflows.
Use of the oncogenicity classifier to streamline filter chains.
Updates to our CancerKB database to include the CancerKB gene track.
Including parallel germline secondary findings for the whole NGS workflow.
User perspective for somatic variant analysis in VSClinical AMP
Somatic analysis is a complex and precise process that is constantly evolving. As the volume of available data and the accessibility of sequencing technology increase, so too does the value of a versatile, well-vetted, and efficient workflow solution. In this webcast, we will take a deep dive into the current state of our AMP interpretation software and explore various ways to optimize workflows. For anyone from grizzled VarSeq veterans to those seeing our software for the first time and labs of any size, we will provide a practical overview of our somatic analysis capabilities and how those capabilities scale with improving technology.
Throughout this webcast we will be discussing the following:
- Universal principles of somatic workflows, providing baseline recommendations
- Specific tumor-normal and somatic-only use cases
- VSClinical AMP interpretation hub and some variants of interest
- Opportunities for automation and how to decrease time to report for increased throughput
Join us as we show off the versatility and scalability of our AMP interpretation capabilities!
CNV Annotations: a crucial step in your variant analysis
Since the development of our NGS-based CNV solutions for VarSeq and SVS, we've generated a long list of content demonstrating simple workflows to help isolate clinically relevant events for a given sample. However, it's just as important to talk about the exclusionary filters that help remove any extraneous CNVs from the analysis.
Golden Helix stands alone in our delivery of multiple methods for filtering down to top-quality, rare, and clinically relevant variants. This webcast will focus on the application of the various CNV annotations, discussing their purpose and usability in quickly removing CNVs with high-population frequency, duplicated regions inherent to the human genome, benign events, and events known in healthy individuals.
Please join us in an exploration of VarSeq's unique CNV annotation capabilities to see how users can overcome the challenges of NGS-based CNV detection.
What will you learn in this webcast?
Initial assessment of sample and CNV event quality
General review and understanding of various CNV annotations in VarSeq
The application of CNV annotations to eliminate common and benign CNVs
Updates to VSClinical ACMG Guidelines & a Tour of Cancer Annotation Sources
Earlier this year we launched our latest product VSClinical featuring workflow support for the ACMG guidelines with advanced automation capabilities and per-criteria recommendations. It has been amazing to watch the adoption of this product in labs doing both germline and in some cases cancer variant interpretation. Our latest VarSeq 2.1 release demonstrates our approach to iterative product improvements based on our engaged relationship with our customers and includes numerous improvements to VSClinical.
In this webcast, we cover the new and updated capabilities that can add value to your genetic testing workflows as well as review the VarSeq workflow support somatic variant interpretation in tumors by leveraging our cancer-specific annotations sources. In this webcast, we:
Demonstrate the new “Consortium Classification” support in VSClinical to have an additional ClinVar-like annotation source added to the automated and interactive ACMG scoring process
See how previous interpretations are integrated into your VSClinical analysis, whether they are for the current variant or are just in the genomic neighborhood
Cover the additional “Lookup in PubMed” variant search feature for finding supporting studies that may provide functional or clinical evidence for a variant
See in action the new ACMG Auto Scoring based templates for trio analysis and gene panel tests
Review somatic variant filtering and prioritizing in VarSeq and the updates to relevant public annotation sources including CiVIC, ICGC and a new and available to license COSMIC v86!
Updates to VSClinical ACMG Guidelines & a Tour of Cancer Annotation Sources
Earlier this year we launched our latest product VSClinical featuring workflow support for the ACMG guidelines with advanced automation capabilities and per-criteria recommendations. It has been amazing to watch the adoption of this product in labs doing both germline and in some cases cancer variant interpretation. Our latest VarSeq 2.1 release demonstrates our approach to iterative product improvements based on our committed relationship with our customers and includes numerous enhancements to VSClinical.
In this webcast, we cover the new and updated capabilities that can add value to your genetic testing workflows as well as review the VarSeq workflow support somatic variant interpretation in tumors by leveraging our cancer-specific annotations sources. In this webcast, we:
-Demonstrate the new “Consortium Classification” support in VSClinical to have an additional ClinVar-like annotation source added to the automated and interactive ACMG scoring process.
-See how previous interpretations are integrated into your VSClinical analysis, whether they are for the current variant or are just in the genomic neighborhood.
-Cover the additional “Lookup in PubMed” variant search feature for finding supporting studies that may provide functional or clinical evidence for a variant.
-See in action the new ACMG Auto Scoring based templates for trio analysis and gene panel tests.
-Review somatic variant filtering and prioritizing in VarSeq and the updates to relevant public annotation sources including CiVIC, ICGC and a new and available to license COSMIC v86!
Enhance Genomic Research with Polygenic Risk Score Calculations in SVS
Golden Helix’s SNP & Variation Suite (SVS) has been used by researchers around the world to do trait analysis and association testing on large cohorts of samples in both humans and other species. The latest SVS release introduces a significant leap in capabilities, with a focus on advanced Polygenic Risk Score (PRS) calculations. PRS has become a fundamental tool in genomic research, enabling the identification of correlations between genotypic variants and phenotypes across large populations.
This enhancement is particularly relevant for researchers working on large cohorts and meta-analysis. Please join us as we explore:
-SVS Workflow Review: A review of the extensive capabilities of SVS to meaningful insights from large cohorts and association test result datasets
-Computing Polygenic Risk Scores: An overview of the PRS capabilities in SVS, including Clumping and Thresholding and creation of multiple PRS models
-Evaluating and Applying PRS: Evaluating PRS models in-sample and out-of-sample and applying PRS models to perform trait prediction
-Future Implications: Brief exploration of how these advancements in SVS could influence future genomic research.
This webcast will explore how SVS facilitates the creation of multiple PRS models from large-scale genomic data, such as those obtained from extensive cohort studies or comprehensive meta-analyses. Join us to discover how these latest updates in SVS are supporting large-scale genomic research.
A User’s Perspective: Somatic Variant Analysis in VarSeq 2.3.0
VarSeq 2.3.0 facilitates the evaluation of a multitude of somatic genomic variations with a more refined user interface to streamline variant evaluation. Our recent webcasts have shown the full range of these newly developed upgrades:
VarSeq 2.3.0: Supporting the Full Spectrum of Genomic Variation
VarSeq 2.3.0: New TSO-500 and Genomic Signature Support in VSClinical AMP
Now, we are showing it all in action from the user’s perspective. This webcast will provide a comprehensive demonstration of performing somatic variation analysis and reporting. We will review how to use workflow automation to expedite the NGS project creation process and report rendering. We will also demonstrate the streamlined capture of knowledge during variant evaluation by leveraging our clinical expert-curated interpretations with the Golden Helix Cancer Knowledge Base (CancerKB).
We hope you will join us to see VarSeq 2.3.0 from a user’s perspective, covering:
-Somatic variant workflows: necessary algorithms and filtering strategies
-Import of all relevant biomarker and genomic signatures data from TSO-500
-Review content and value of clinically curated interpretations and treatments with CancerKB
-Interpretation of structural variants in the VSClinical AMP Guidelines workflow
-Workflow automation with VSPipeline
Automated FASTQ to Reports with VarSeq Suite: A fast, flexible solution
NGS tests in the clinic cover more use cases than ever and are increasingly complex to implement. This leads to an increase in time to validate and bring tests to production, impacting a lab’s ability to be economically viable and serve the needs of patients. Core to the complexity is the expansion of tests to include multiple types of biomarkers and variants, including CNVs, gene fusions, and genomic signatures. The bioinformatics demands of these pipelines require powerful tools with built-in capabilities to handle the diverse needs of modern NGS tests and to integrate and automate the disparate steps leading to clinical insight.
Join us in this webinar as we explore the VarSeq suites’ capabilities as a fast, modular, and highly configurable solution for variant analysis and interpretation. We will cover:
The bioinformatic diversity of comprehensive genetic tests with NGS
Automation of FASTQ to clinical reports without losing control over the results of a test
Leverage built-in and custom automation capabilities in the VSClinical cancer guideline workflow to reduce work and improve accuracy
Reporting the relevant diagnostic and therapeutic findings for a patient based on the raw genomic data of modern NGS tests requires both human experience and advanced analysis software. We hope you can join us as we unpack how automation is a critical part of implementing NGS tests and furthering the application of precision medicine.
Maximizing the Benefits of Comprehensive Genomic Testing in Cancer Care with ...
Comprehensive genomic testing via next generation sequencing (NGS) is being increasingly adapted as part of cancer care in conjunction with molecular and immunohistochemical tests. Comprehensive genomic profiling potentially expands the number of targeted therapies that are available to patients, improves patient diagnosis and prognosis, and increases the number of clinical trials that are relevant to patients. However, with these advancements come challenges such as gaps in expertise resulting in inadequate efforts to interpret genomic data accurately and efficiently, poorly coordinated efforts to implement precision care, patients being diagnosed and treated despite inadequate access to relevant information and subsequent lack of patient exposure to all available treatment options.
Golden Helix CancerKB v2.0 provides a means of closing the gap, whether you're a beginner who is trying to capture the vast amount of knowledge in the cancer field or an expert who has high sample volume AND needs to keep up with the ever-evolving knowledge of Tier II and III variants. In this webcast, we will discuss and apply Golden Helix CancerKB in the context of cancer precision medicine. Golden Helix CancerKB is systematically curated and reviewed by experts in the field and contains information about cancer genes, biomarkers, and treatments generated from several trusted cancer resources. With VarSeq 2.3.0’s added support for comprehensive cancer genomic profiling tests, Golden Helix CancerKB has expanded to include interpretations for genomic signatures, combination biomarkers, and more investigational (tier II) biomarkers, among several other additions that will be discussed. With the Golden Helix CancerKB database, users will experience a streamlined automatic matching of biomarkers to available drugs and trials which ultimately saves users massive amounts of time and effort while reducing the possibility for errors.
Next Generation Companion Diagnostics; Adoption, Drivers, and Moderators of N...
Analysis and synthesis of a pulse survey conducted across >140 oncologists, pathologists, and lab directors regarding current adoption and trends associated with emerging oncology biomarkers and companion diagnostics (CDx), with an emphasis on next-generation sequencing (NGS)-based CDx.
Exome Analysis with VS-CNV and VSClinical: Updated Strategies and Expanded Ca...
As exome sequencing continues to gain momentum as a comprehensive and affordable genetic test, many labs are considering the transition from their various targeted gene panels to a single comprehensive exome test. Along with the various challenges in small-variant analysis and interpretation of exomes, CNVs also require exome-specific considerations and strategies. In this webcast, we will review new capabilities and updated algorithms in the latest VarSeq release that will assist in any clinical exome sequencing workflow. Please join us in this webcast, as we review:
A new VS-CNV best-practice workflow with specialized features for calling CNVs on exomes and large panels with more precision, enhanced quality flags and additional outputs.
Enhanced analysis of variants found in exome sequencing, including non-coding clinically relevant RNA variants and mitochondrial variants
Additional CNV analysis capabilities such as CNV export and import as VCFs
The identification and interpretation of easily missed variants, such as those introducing novel splice-sites using the ACMG auto-classification and interpretation workflow
Strategies for incorporating disease-specific virtual gene panel lists into the filtering, quality and reporting capabilities of VSClinical
Exome sequence analysis is complex, and the process to define and validate a clinical exome test can be daunting. The VarSeq clinical suite has the flexibility and best practice workflows built-in to define and implement a repeatable and comprehensive workflow for CNVs detection and analysis by exome sequencing. We hope you can join this webinar to learn how to go from FASTQ to clinical reports for exome-based clinical tests.
Building Secure Analysis and Storage Systems with Golden Helix
Genetic testing labs deal with personal data in categories with the highest level of security requirements: personal identity and medical records. Given the liability and risk associated with a breach of this secure information, it is not surprising that many labs and institutes that aggregate genomic data prefer if not require on-premise analysis and storage solutions.
Golden Helix is in a unique position to provide completely on-premise analysis solutions with a history of building analysis software from the ground-up on first principles and a focus on providing integrated, turn-key solutions. This allows for a licensing model based on training and supporting users, not tracking per-sample usage of cloud resources. As the regulatory environment around the world strengthens the privacy rights of individuals and the outcry around data breaches raises the stakes for building a secure system, we have developed a number of best practices for building secure, offline genomic analysis pipelines. Watch as we cover:
- Building a FASTQ to clinical reports pipeline behind a firewall
- On-premise analysis, warehouse and data servers independent of the internet
- Single sign-on based on local credential systems and without internet access
- Storage and network considerations for the analysis of patient-linked data
- Choose when to update and validate new pipelines, data sources and software versions
We hope you enjoy as we review the capabilities and best practices in building the most secure environment for hosting the analytics behind your precision medicine tests.
Efficient Application of NGS Family-Based Analysis
Golden Helix is committed to providing next-gen sequencing solutions that are comprehensive and efficient. A significant portion of our user base processes pediatric cases or requires the ability to run family-based analyses that can be applied to all inheritance models in order to identify rare variants in Mendelian disorders and cancer. To increase diagnostic yield and reduce time to clinical results, these models and workflows must be easy to set up and used efficiently. Optimization can involve all the steps, including data import, workflow design (variant filtering), a detailed evaluation of variant impact and clinical relevance via ACMG guidelines and AMP guidelines, as well as providing a full clinical report.
VarSeq is the best tool to accomplish this task. VarSeq, our tertiary analytics platform, is designed to process all sizes of genomic data. It can filter through all variants in order to identify clinically relevant variants. The results are evaluated using automated and standardized guidelines. This webcast will demonstrate workflows tailored to different pedigree scenarios. It will also demonstrate VarSeq features designed to speed up analysis time while maintaining consistency with outcomes.
In this webcast, we will cover the following topics:
Explore various family-based project designs (includes trio and duo & extended families)
Discuss various inheritance models (compound het, de novo, dominant inherited, etc)
Briefly examine the ACMG guidelines relevant to inheritance and review an example trio clinical report
Demonstrate how VSPipeline can automate the creation of projects
VarSeq 2.5.0: Empowering Family Planning through Carrier Screening Analysis
Over the past 50 years, partners with potential genetic risks have sought advanced genetic testing to guide family planning decisions. Carrier screening is a valuable tool in genetics and reproductive medicine that helps individuals and families make informed choices about family planning and reduce the risk of passing autosomal recessive or X-linked genetic disorders to their children. Several carrier screening panels are available for Next-Generation Sequencing platforms, ranging from those targeting prevalent disorders to expanded ones covering various inherited conditions. Since NGS offers an affordable, high-throughput solution, carrier screening has become a common practice in healthcare systems.
We are excited to announce that VarSeq and VSClinical now support a multi-sample carrier screening workflow. VarSeq 2.5.0 unlocks the ability to:
-Filter variants between samples and identify genes in which a variant from each partner sample is present.
-Apply the ACMG Carrier Screening gene panel or generate customized carrier screening panels to include in your analysis.
-Evaluate partnered samples side-by-side in a single VSClinical evaluation.
-Generate a combined sample clinical report that includes reproductive risk calculations for the most prevalent autosomal recessive and X-linked diseases.
Similar to Clinical Validation of Copy Number Variants Using the AMP Guidelines (20)
Efficiently Following the AMP Guidelines with VSClinical and Golden Helix Can...
Efficiently Following the AMP Guidelines with VSClinical and Golden Helix Can...
VarSeq 2.3.0: New TSO-500 and Genomic Signature Support in VSClinical AMP
VarSeq 2.3.0: New TSO-500 and Genomic Signature Support in VSClinical AMP
VarSeq 2.5.0: VSClinical AMP Workflow from the User Perspective
VarSeq 2.5.0: VSClinical AMP Workflow from the User Perspective
User perspective for somatic variant analysis in VSClinical AMP
User perspective for somatic variant analysis in VSClinical AMP
CNV Annotations: a crucial step in your variant analysis
CNV Annotations: a crucial step in your variant analysis
Updates to VSClinical ACMG Guidelines & a Tour of Cancer Annotation Sources
Updates to VSClinical ACMG Guidelines & a Tour of Cancer Annotation Sources
Updates to VSClinical ACMG Guidelines & a Tour of Cancer Annotation Sources
Updates to VSClinical ACMG Guidelines & a Tour of Cancer Annotation Sources
Enhance Genomic Research with Polygenic Risk Score Calculations in SVS
Enhance Genomic Research with Polygenic Risk Score Calculations in SVS
A User’s Perspective: Somatic Variant Analysis in VarSeq 2.3.0
A User’s Perspective: Somatic Variant Analysis in VarSeq 2.3.0
Automated FASTQ to Reports with VarSeq Suite: A fast, flexible solution
Automated FASTQ to Reports with VarSeq Suite: A fast, flexible solution
Maximizing the Benefits of Comprehensive Genomic Testing in Cancer Care with ...
Maximizing the Benefits of Comprehensive Genomic Testing in Cancer Care with ...
Next Generation Companion Diagnostics; Adoption, Drivers, and Moderators of N...
Next Generation Companion Diagnostics; Adoption, Drivers, and Moderators of N...
Exome Analysis with VS-CNV and VSClinical: Updated Strategies and Expanded Ca...
Exome Analysis with VS-CNV and VSClinical: Updated Strategies and Expanded Ca...
Building Secure Analysis and Storage Systems with Golden Helix
Building Secure Analysis and Storage Systems with Golden Helix
Efficient Application of NGS Family-Based Analysis
Efficient Application of NGS Family-Based Analysis
VarSeq 2.5.0: Empowering Family Planning through Carrier Screening Analysis
VarSeq 2.5.0: Empowering Family Planning through Carrier Screening Analysis
From Clinical Decision Support to Precision Medicine
From Clinical Decision Support to Precision Medicine
More from Golden Helix
Introducing VarSeq Dx as a Medical Device in the European Union
A transition period regarding in vitro medical device (IVD) regulation in the European Union (EU) is upon us. The former IVDD regulations are phasing out and IVDR 2017/746 has already taken its place as the acting regulation for IVD manufacturers but also lab developed tests (LDTs) and health institutions. In our upcoming webcast we will talk about the roles and significance of IVDR and ISO 13485 certification for clinical labs and for Golden Helix as a medical device manufacturer.
Join us as we will introduce VarSeq 2.6.1 complete with Dx Mode, which offers the use of VarSeq as CE marked medical device. Even more we will also present strategies to facilitate the transition of Golden Helix customers to operate in accordance with IVDR.
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
In the rapidly evolving field of genomic analysis, staying current with the latest research, data sources, and test advancements is crucial. In this webinar, we review how VarSeq addresses the needs to stay on top of the latest with the release of VarSeq 2.6.0.
This release features an exome-optimized workflow for LOH and CNV calling as well as the introduction of VSPGx to produce pharmacogenomic reports for gene panels as well as exomes and genomes. With the recent release of gnomAD v4, we have had many requests for the integration of this large update to the most population frequency source. With VarSeq 2.6.0, the latest version of gnomAD has been integrated into VSClinical and the updated tracks spans beyond variants to cover CNVs and gene scores to update all your workflows to the latest data.
In this webcast, we will cover.
Improved VS-CNV performance and updated exome analysis workflows.
Pharmacogenomics in action: Utilizing VSPGx for exome and genome assessments.
gnomAD v4 in practice: Updated automated and manual variant interpretation workflows.
Join us for an insightful session on the latest VarSeq 2.6.0 features, bringing you the most up-to-date data and workflows for your genomic analysis.
Introducing VSPGx: Pharmacogenomics Testing in VarSeq
Inter-individual variability in drug response poses a significant challenge for clinicians, with much of this variability resulting from inherited genetic differences. While the field of pharmacogenomics (PGx) can provide powerful insights into how genomic factors affect drug response, the implementation of PGx testing in the clinic is hampered by the difficulty of translating genetic test results into actionable recommendations. In this webcast, we will discuss VarSeq’s new PGx testing capabilities, including the ability to identify actionable pharmacogenomic diplotypes and generate clinical reports.
In this webcast you will learn:
-How to identify pharmacogenomic diplotypes and drug recommendations from NGS data.
-How to incorporate externally called CNVs and SVs into your PGx annotations.
-How to generate customizable PGx reports from these annotations.
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...
Clinical Whole Exome Sequencing (WES) offers a high diagnostic yield test by detecting pathogenic variants in all coding genes of the human genome. WES is poised to consolidate multiple genetic tests by accurately identifying Copy Number Variation (CNV) events, typically necessitating microarray analyses. However, standard commercial exome kits are limited to targeting exon coding regions, leaving significant gaps in coverage between genes which could hinder comprehensive CNV detection.
Addressing the need for comprehensive coverage, Twist Bioscience has developed an enhanced Twist Exome 2.0 Plus Comprehensive Exome Spike-in capture panel with added "backbone" probes. These probes target common SNPs polymorphic in multiple populations and are evenly distributed in the intergenic and intronic regions, with three varying densities at 25kb, 50kb, and 100kb intervals. In this webcast, we discuss the combined efficacy of the backbone-probe enhanced exome capture kit and VS-CNV in identifying known CNVs using the Coriell CNVPANEL01 reference set.
This webcast reviews:
-The sensitivity rate for the detection of known CNV events at all three probe densities.
-The impact of best-practice quality metrics and filters on sensitivity.
-How VarSeq’s CNV annotation capabilities can be leveraged to identify likely pathogenic CNVs.
-The interpretation of clinically relevant CNVs using VSClinical.
From Panels to Genomes with VarSeq: The Complete Tertiary Platform for Short ...
From gene panels to whole genome, from short to long-read sequencing, the VarSeq suite is the solution for NGS analysis and reporting in a modern clinical lab. VarSeq handles the spectrum of variant types (SNV, Indel, CNV, Fusions) and provides automated classification and reporting capabilities following the ACMG and AMP guidelines. With our new PacBio partnership, we are more adaptable than ever with creating a spectrum of custom workflows to suit our unique user needs.
This webcast will review:
-Data analysis scaling from Gene Panel to Genome analysis with VarSeq and VSWarehouse.
-Analysis and annotation of SNVs, Indels, CNVs, and fusions.
-A close look at a PacBio long-read trio analysis.
Come join us for this showcase in modern VarSeq analysis capabilities.
Identifying Oncogenic Variants in VarSeq
The interpretation of somatic variants can be a challenging process. While AMP Guidelines provide detailed rules for accessing the clinical evidence associated with a specific variation, they do not specify criteria for determining if a variant is likely to be a driver mutation, which generates functional changes that enhance tumor cell proliferation. In this webcast, we will discuss a new VarSeq algorithm for estimating the oncogenicity of a variant. This will include a deep dive into our oncogenicity scoring system and a discussion of the various criteria used to distinguish driver mutations from benign variations and variants of uncertain significance.
What you will learn in this webcast:
-How to use the scoring algorithm to identify variants with evidence of oncogenicity
-Which criteria are used to assess a variant's oncogenicity
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Best Practices for Validating a Next-Gen Sequencing Workflow
Validating an NGS workflow is an iterative process that begins with collaboration with personnel and planning protocols for the entire workflow from sample preparation, sequencing and variant calling, all the way to data analysis and reporting. At Golden Helix, while we do not provide pre-validated black-box workflows, we provide our customers with support to validate workflows in a transparent manner, and assist them in reaching production deadlines. This webcast will be led by members of our Field Application Scientist team, and we will explore some of the best practices for NGS workflow validation that we have observed and helped to implement based on real-world examples from our customer base. Key topics for discussion will include:
Sample preparation and collection of adequate case/control data
Designing a robust workflow with special considerations for single versus family analyses and phenotypic considerations
Generating the desired output for clinical or other reports
Real world NGS workflow validation strategies
Tune in for tips and strategies that you can deploy when designing and validating your NGS workflow.
2023 Innovation Awards Winner, Dr. Muthukumaran
Expanded carrier screening in an infertile/affected Couple for determining carrier status for genetic mutations - VarSeq Couple Carrier Workflow
VarSeq 2.4.0: VSClinical ACMG Workflow from the User Perspective
Earlier this year, we released VarSeq 2.3.0 which brought massive updates to our VSClinical AMP interface, such as enhanced capabilities for automation and analysis of structural variants in the cancer context. Naturally, we wanted to follow that up shortly with similar advancements to our VSClinical ACMG interface, and also make our customers doing germline variant analysis happy.
Our latest software release, VarSeq 2.4.0, was therefore focused on the advancements in VSClinical ACMG, namely support for importing and clinically evaluating structural variants, long read sequencing, advanced automation with evaluation scripts in VSClinical ACMG and end-to-end automation of ACMG workflows with VSPipeline. These new and improved features were discussed in a great webcast by our VP of Product and Engineering, Gabe Rudy, last month.
This upcoming webcast by our FAS team will be a user’s perspective on the new features in VarSeq 2.4.0 and VSClinical ACMG and how our tools can precisely and efficiently enable the full spectrum NGS analysis for Mendelian disorders.
VarSeq 2.4.0: Structural Variants and Advanced Automation in VSClinical ACMG
Mendelian disorders can be caused by various classes of genetic mutations, from small variants to CNVs and even Structural Variants. With the introduction of VarSeq 2.4.0, we are excited to unveil the latest advancements in VSClinical ACMG, focusing on the integration of Structural Variants and the enhanced automation capabilities that streamline your analysis process.
Join us in this webcast as we dive into the following topics:
Integration of Structural Variants: Learn how VarSeq 2.4.0 enables you to import and incorporate Structural Variants into your VSClinical ACMG evaluations and reports, providing a comprehensive understanding of the genetic landscape.
Advanced Automation in the ACMG Interface: Discover how evaluation scripts can be employed to automate the VSClinical ACMG interface, allowing you to perform custom actions or eliminate manual steps, thus increasing efficiency and reducing the risk of errors.
End-to-End Automation: Explore how VSPipeline can fully automate your analysis process, from raw VCF to report, ensuring a streamlined and consistent workflow that saves time and resources.
Harnessing the Power of VSClinical: Gain insights into how VarSeq 2.4.0 empowers you to tackle complex genomic data, enabling faster and more accurate identification of Mendelian disorders and facilitating personalized patient care.
With the advanced capabilities of VarSeq 2.4.0 and VSClinical, you can now unlock a new level of precision and efficiency in diagnosing Mendelian disorders. This webcast will showcase the latest innovations in variant interpretation and automation, exemplifying why the VarSeq Clinical Suite is the premier NGS analysis platform for germline and cancer testing.
The Wide Spectrum of Next-Generation Sequencing Assays with VarSeq
There is a strong motivation for labs to bring most, if not all, of their next-gen sequencing pipeline in-house. This is especially relevant for clinical applications where there is a need to validate any routine diagnostics when seeking to provide genetic results to patients. The entirety of the NGS pipeline is highly automatable and comprised of multiple stages but from the geneticist's point of view, the tertiary stage requires the lengthiest review. This stage is where the geneticist sifts through the massive collection of genetic variants to find and report on those most relevant to the patient or population. Unfortunately, the tertiary stage can be a fairly sophisticated process and there aren’t many tools on the market that handle it comprehensively and simply. Many of the tools that are available may have severe limitations on the scale of genomic data they can process or limitations on the types of NGS assays that can be designed. Moreover, their license model may be on an individual sample basis and present cost-benefit hurdles for the user, especially when sample load will inevitably increase. Fortunately, none of these assay or cost-based issues are relevant with Golden Helix products.
The goal of this webcast is to expose our viewers to the versatility that GHI VarSeq provides when constructing your dream NGS assay. This demonstration will provide examples of germline and somatic workflows for both single and multi-sample analysis for a variety of different disorders. Please join us and learn more about the analytical possibilities you can achieve when using the VarSeq software.
Prenatal Genetic Screening with VarSeq
Our past webcast explored the current approaches for screening and diagnosis of genetic disorders in prenatal testing. While the methods available at the time were robust, they were severely limited, creating a need for a higher diagnostic yield and more efficient analysis for a wider range of genetic tests. The solution proposed was to improve and simplify prenatal screening and diagnosis with whole exome sequencing (WES).
During that webcast, we highlighted the advantages of WES over traditional methods such as karyotyping and chromosomal microarray, including improved accuracy, granularity, and cost-effectiveness. We also emphasized the potential of WES to expand diagnosis for many other adverse maternal-fetal complications beyond the large aneuploidy events previously covered. However, there was still an intimidation factor when it came to the massive data output from the exome. Fortunately, Golden Helix provided the necessary tools to build and standardize these genetic assays, simplifying the analytical process while leveraging increased diagnostic output. We explored our VarSeq software to demonstrate some example workflows of cases positive for Trisomy 21, an exon loss in DMD related to Duchenne Muscular Dystrophy, and detection of a single base change resulting in a LOF variant in RUNX1 relevant to hereditary leukemia.
Our goal was to expose our viewers to the methods of conquering this vast NGS-based data and play a role in dissolving any feeling of intimidation. Overall, exome sequencing has the potential to vastly improve diagnostic outcomes and widen discoveries in the research related to prenatal testing, and Golden Helix products are designed to facilitate this process.
VarSeq 2.3.0: Supporting the Full Spectrum of Genomic Variation
Next Generation Sequencing allows for the detection of a wide variety of genomic alterations. This includes small mutations, copy number variants and complex rearrangements. However, it can be difficult to annotate, filter, and interpret these alterations.
As part of our VarSeq 2.3.0 release, we have greatly simplified this process by allowing you to import, annotate, and filter mutations across all spectrums of genomic variation. This supports concurrent importation of small variants and CNVs as well as complex rearrangements. This release also includes strong support for structural variant annotation, filtering, and interpretation, including structural variant effect prediction. After filtering is complete, any clinically relevant structural variants can be interpreted with the VSClinical AMP Guidelines workflow and included in the final clinical report.
Come join us for this webcast to discuss VarSeq’s enhanced import and annotation capabilities, including:
Concurrent importation of variants CNVs and complex rearrangements
Improved multi-threaded import which dramatically speeds up the importation of large VCFs
Annotation of structural variants and prediction of effect
Interpretation of structural variants in the VSClinical AMP Guidelines workflow
Support for visualization and use of CRAM files as input for computing coverage statistics
Single Sample and Family Based Genome Analysis With VarSeq
One major hurdle facing medicine is the need to quickly identify and assess the genetic components contributing to rare diseases. It has been estimated that nearly 350 million people suffer from rare diseases, 140 million of which are children, of whom ~30% do not live past their fifth birthday1,2. The specific issue to overcome is reducing morbidity by facilitating rapid diagnosis and treatment. Fortunately, the cost of whole genome sequencing has dropped below the $1000 mark, which not only makes the NGS approach more affordable but has become the status quo method of comprehensive diagnosis for these rare disorders. Currently, there are limited options in the market when it comes to quality software that can scale to this size of data and handle variant processing and evaluation in a timely fashion. Fortunately, Golden Helix has sought to set the market standard for top-quality NGS analysis with our bioinformatic software VarSeq. The focus of this webcast will be to explore example workflows tailored for rare disorders and elaborate on how best to expedite the NGS pipeline process with our command-line tool VSPipeline.
During the webcast, we will address the following:
Customizing clinically validated NGS workflows with VarSeq for both single sample and trios
Demonstrating the automation of ACMG-based guideline review in the VSClinical variant interpretation hub and rendering of customized clinical reports
Expediting the NGS workflow via Golden Helix command-line tool VSPipeline
We look forward to you joining us for our presentation, where we can demonstrate the value of our products when building your next-gen workflows. Ultimately, we wish to diminish the intimidation of genome workflow design and leave our future customers feeling confident that there is capable software to suit their needs.
Bick D, Jones M, Taylor SL, et al. Case for genome sequencing in infants and children with rare, undiagnosed or genetic disease. J Med Genet 2019; 56:783-791.
Owen M, Lefebvre S, Hansen C, et al. An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases. Nat Commun 2022; 13: 4057. https://doi.org/10.1038/s41467-022-31446-6
Maximizing Profitability in your NGS Testing Lab
The automation of clinical NGS workflows provides a number of important benefits for labs. Automation reduces the time required to produce a clinical report, mitigates the possibility of human error, and improves the precision of clinical results. In turn, these benefits create higher profitability from a P&L perspective.
Golden Helix software is designed to meet these needs by automating the full analysis workflow from sequencer to clinical report on a fixed annual subscription model. We are looking forward to discussing the best practices of maximizing profitability in your NGS testing lab and how Golden Helix supports these efforts.
Join us in this webinar as we cover how to develop repeatable cancer and germline interpretation workflows that scale from panels to whole exomes and genomes.
Handling a Variety of CNV Caller Inputs with VarSeq
VarSeq has become renowned for the accuracy of its CNV Caller, and the ease with which VSClinical takes the user through CNV evaluation. Cited in many publications, this well-validated tool brings our customers the ability to run both variant and CNV interpretations in one program, on data ranging from Gene Panels to whole genomes. What is less well known about CNV analysis through VarSeq, is that our users are not only limited to CNVs called through our software. VarSeq CNV is able to import CNVs in several file formats (VCFs, text, or tsv) generated by a wide variety of secondary callers, allowing the user to analyze their externally derived data. In this webcast, we will take you through the basics of CNV analysis with both the VarSeq CNV caller and from several common external CNV callers.
Join us in this webinar as we cover:
Leveraging the Copy Number Probability and Segregation Algorithm to add power to a CNV Trio workflow.
Importing externally called CNVs.
Expediting the path to analysis with CNV specific templates.
Utilizing the auto-recommendations to efficiently analyze the pathogenicity of several CNV calls and generate clinical reports.
Evaluating Cloud vs On-Premises for NGS Clinical Workflows
In the era where cloud-based solutions are the default for the modern office, it may not be obvious why many laboratories and testing centers choose to host their data and analysis pipelines on-premises or on self-managed cloud services. Next-generation sequencing enables a precision medicine approach to rare disease diagnostic and cancer therapeutics through its power to detect unique variants in individuals. This data is generated quickly and cheaply but requires a lot of disk space and processing power to arrive at clinically useful insights.
When providing a clinical lab service under a regulated environment: data security, long-term affordable storage, and versioning through locked-down pipelines are all factors that must go into the choice of whether to choose a hosted analytics platform versus on-premises solutions or self-managed cloud infrastructure.
Join us in this webinar as we cover:
The validation and regulatory requirements that inform infrastructure and hosting decisions for NGS labs
The cost structure of scaling NGS labs to exomes and genomes
Deployment and security architecture for on-premises and self-managed cloud infrastructure
Validating and versioning analysis pipelines with clinical tests through self-managed software lifecycles and versioned annotation sources
Cybersecurity, patient data privacy, and scalable unit economics play a bigger role than ever before in the planning of NGS lab’s infrastructure choices. We look forward to you joining us as we tackle the trade-offs and choices around these topics and how deployment flexibility is a core feature of the Golden Helix VarSeq Suite.
VarSeq Custom Database Curation Capabilities.pdf
As our users have come to know, VarSeq serves as a hub for variant annotation and the full interpretation/classification of germline (ACMG) and somatic (AMP) variants. Whether direct annotation or backend variant evidence is being presented to the user via VSClinical for the interpretation process, users greatly benefit from the hosted variant databases being available directly from VarSeq. Our team has automated much of the curation process and hosts the ongoing updates to these tracks so that users no longer suffer manual review of each database via the web or manual curation efforts. Useful databases include ClinVar and ClinGen for classification submissions, gnomAD exomes/genomes for filtering out common variants in the population, RefSeq for gene impact and sequence ontology assessment, and OMIM for phenotypic information. Obviously, there is a large collection of databases out there, and not all of them make it into our automated queue. However, GHI supports the utilization of custom databases in our software. This webcast will expose features of custom database curation/utilization in VarSeq to optimize your NGS workflows even further.
During the presentation, we will discuss many different approaches with custom annotations, including:
Interval Tracks: Bed files defining target regions for coverage calculations and CNV detection.
Assessment catalogs: record keeping of variant classification/interpretations in VSClinical.
Frequency catalogs: approaches to capture all variant allele frequencies at a project level and cohort level with VSWarehouse.
Automating Clinical Workflows with the VarSeq Suite
The automation of clinical NGS workflows provides a number of important benefits. Automation reduces the time required to produce a clinical report, mitigates the possibility of human error, and improves the precision of clinical results. In this webcast, we will discuss how the VarSeq Suite can be leveraged to automate the full analysis workflow from sequencer to clinical report. Join us as we demonstrate how VarSeq’s automation capabilities can enable your laboratory to:
Automatically perform secondary analysis when a new sequence run is complete
Go from FASTQ to BAM and high-quality variants in VCFs using Sentieon
Automatically start VSPipeline to go from raw VCFs to candidate variants
Compute coverage and call CNVs alongside small variants with VS-CNV
Efficiently interpret a small set of annotated candidate variants and CNVs
Draft reports with VarSeq and VSClinical
Join us as we discuss the automation of the clinical analysis process for NGS genetic tests from FASTQ to Clinical Reports using the VarSeq Suite and discover how your laboratory’s NGS workflows may benefit from these automation capabilities.
Integrating Custom Gene Panels for Variant Innovations
The ability to use predefined sets of genes to isolate clinically relevant variants is an important aspect of clinical variant analysis. Golden Helix’s VarSeq product houses the tools, namely our Gene Panel Manager and Match Genes set of algorithms, that enable users to create and manage reusable gene lists within projects, incorporate the ACMG Secondary Findings v3.0 gene list for the reporting of incidental findings, make use of well validated publicly available gene panels with published evidence of disease associations and create gene panels based on specific disorders or phenotypes of interest. These capabilities were covered in a webcast “Creating and Managing Reusable Gene Lists with VSClinical” by Dr. Nathan Fortier our Director of Research. In the upcoming webcast, we will dive deeper into these capabilities, implementing our gene panel tools from the user’s perspective by focusing on two clinical use cases where custom virtual gene panels are particularly useful.
For the standard use case, users typically incorporate targeted gene panel-based data to hone in on any number of variants that fall within the scope of their targeted genes list. More recently, we have observed from the field application perspective, a trend among Golden Helix customers towards importing WES and WGS data followed by creating unique per sample gene panels. Therefore, the purpose of this webcast will be to showcase how simple it can be to construct and manage both styles of virtual gene panels within VarSeq in ways that will best suit the specific needs of your lab. We will share with you several clever shortcuts for users to implement filters on gene panels, to design and manage gene panels and calculate the coverage over these regions. We will also delve into the details of incorporating gene panel data into variant evaluation in VSClinical and bringing the relevant information into a final clinical report. Viewers tuning in to this webcast will be exposed to all the tools available in VarSeq for creating and managing their potential gene panel workflows.
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Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
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According to WHO,
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VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
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CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
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BOWEL ELIMINATION BY ANUSHRI SRIVASTAVA.pptx
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
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Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
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DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
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- 1. Clinical Validation of Copy Number Variants Using the AMP Guidelines Dr. Eli Sward – Field Application Scientist sward@goldenhelix.com 20 Most Promising Biotech Technology Providers Top 10 Analytics Solution Providers
- 3. NIH Grant Funding Acknowledgments • Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under: • Award Number R43GM128485-01 • Award Number R43GM128485-02 • Award Number 2R44 GM125432-01 • Award Number 2R44 GM125432-02 • Montana SMIR/STTR Matching Funds Program Grant Agreement Number 19-51-RCSBIR-005 • PI is Dr. Andreas Scherer, CEO Golden Helix. • The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- 4. Filtering and Annotation ACMG & AMP Guidelines Clinical Reports CNV Analysis Pipeline: Run Workflows Variant Warehouse Centralized Annotations Hosted Reports Sharing and Integration CNV Analysis GWAS | Genomic Prediction Large-N Population Studies RNA-Seq Large-N CNV-Analysis Who Are We? Golden Helix is a global bioinformatics company founded in 1998
- 5. Cited in 1,000s of Peer-Reviewed Publications
- 6. Over 400 Customers Globally
- 7. SIMPLE, SUBSCRIPTION- BASED BUSINESS MODEL o Yearly fee o Unlimited training & support SOFTWARE IS VETTED o 20,000+ users at 400+ organizations o Quality & feedback DEEPLY ENGRAINED IN SCIENTIFIC COMMUNITY o Give back to the community o Contribute content and support INNOVATIVE SOFTWARE SOLUTIONS o Cited in 1,000s of publications When you choose Golden Helix, you receive more than just the software
- 9. Power of NGS CNV Detection Small:1 50b+ Medium: 1 – 10Kb Large: 10Kb+ Gene panel Whole exome Whole genome MLPA ✓ ✓ CMA ✓ ✓ VS-CNV ✓ ✓ ✓ ✓ ✓ ✓ Detectable events Supported Data types ▪ One single testing paradigm ▪ True simplification of clinical workflow ▪ Saves time and money – all on site
- 10. Addressing Issues - CNV Detection via NGS ▪ CNVs detected from coverage data in BAM ▪ Challenges • Coverage varies between samples • Coverage fluctuates between targets • *Systematic biases impact coverage ▪ Solutions • Data Normalization • Reference Sample Comparison • Algorithm works without case/control data ▪ Requirements • ≥ 30 ref samples • From same library prep method • Ideally ≥100X coverage
- 11. CNV Detection ▪ Metrics • Ratio: normalized sample coverage divided by the average normalized reference sample coverage • Z-score: standard deviations from reference sample mean • Confidence • P-value is produced for all called events and can be customized to determine the probability that the CNV event is true • Annotations • Population catalogs • SuperDups • Classification
- 12. 225+ Users and 15+ Publications • Journals • Atherosclerosis • Journal of lipid research • Journal of Clinical Lipidology • American Journal of Medical Genetics • BMC Medical Genomics • Medicine • Analysis topics • Hypercholesterolemia • Retinal dystrophy • Pituitary hormone deficiency • Rare Mendelian disorders • Lacocca et al. • Whole exome CNV detection comparison • 100% concordance MLP&CMA with VSCNV • Improves resources, cost, analysis time
- 13. • Automates both ACMG and AMP Guidelines all in one suite • Single nucleotide variants, insertions and deletions, copy number variants, gene fusions • Creates consistency in evaluations / reduces workflow fatigue • Educational purposes • Word-based reporting capabilities Germline Somatic
- 14. Tier I: Variants of Strong Clinical Significance Therapeutic, prognostic & diagnostic Level A Evidence FDA-approved therapy Included in professional guidelines Level B Evidence Well-powered studies with consensus from experts in the field Tier II: Variants of Potential Clinical Significance Therapeutic, prognostic & diagnostic Level C Evidence FDA-approved therapy for different tumor types or investigational therapies Multiple small published studies with some consensus Level D Evidence Preclinical trials or a few case reports without consensus Tier III: Variants of Unknown Clinical Significance Not observed at a significant allele frequency in the general or specific subpopulation database, or pan-cancer or tumor-specific variant database No convincing published evidence of cancer association Tier IV: Benign or Likely Benign Variants Observed at a significant allele frequency in the general or specific subpopulation databases No existing published evidence of cancer association (2017) Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: VSClinical - AMP Guidelines: Biomarkers ▪ Biomarkers: - Biological states with indications for treatments, prognostic, or diagnostic outcomes ▪ AMP Guidelines: 4 Tiers - Tier 1: FDA-approved therapy - Tier 2: FDA-approved for different tumor type / Preclinical - Tier 3: No evidence of cancer association - Tier 4: High allele frequency variants
- 15. AMP Guidelines – Annotations Population Database to exclude common variants Cancer Specific Databases Sequence Repositories Clinical, Drug, and Prediction annotations Splice Site and Functional Prediction Algorithms
- 16. VSClinical AMP: Golden Helix CancerKB Haroche J. et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood 2013 121 ▪ Interpretations for Cancer Biomarkers - Biomarker and Gene interpretations - Assess drug sensitivity, resistance, prognostic, and diagnostic information - Build biomarker classification and interpretation ▪ Updated by users and reviewed by expert panel ▪ Jumpstarts interpretation enhances knowledge base and productivity to final report
- 17. VSClinical – Clinical Report • VSClinical conducts the clinical variant analysis based on ACMG and AMP guidelines - Automated population of the clinical report-based workflow outcome - Standardizing of variant level interpretation based on customizable assessment catalogs - For somatic variants, GHI provides predefined clinical assessments via our CancerKB catalog • Rendering of clinical reports within seconds • Supported output formats - Word - PDF
- 18. VSClinical – AMP Guidelines: Project Demonstration • CNV background - ~ 50 Reference samples - Predefined workflow - Quality/Confidence filtering - Remove common CNVs - Targeted phenotype • Evaluate CNV in VSClinical – AMP hub - Patient info - Mutation selection - Biomarker interpretation + treatment options - Clinical report
- 20. NIH Grant Funding Acknowledgments • Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under: • Award Number R43GM128485-01 • Award Number R43GM128485-02 • Award Number 2R44 GM125432-01 • Award Number 2R44 GM125432-02 • Montana SMIR/STTR Matching Funds Program Grant Agreement Number 19-51-RCSBIR-005 • PI is Dr. Andreas Scherer, CEO Golden Helix. • The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- 22. CoLab Discussions: Wednesday, Oct 16th - 12:45-1:30pm | Clinical Variant Analysis: Applying the AMP & ACMG Guidelines in the Clinical Practice Thursday, Oct 17th - 12:45-1:30pm | State of the Art Clinical Copy Number Variant Analysis in Next- Gen Sequencing Data: Gene Panels, Whole Exome, Whole Genome
- 24. Additional Questions? info@goldenhelix.com | goldenhelix.com