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.
From Panels to Genomes with VarSeq: The Complete Tertiary Platform for Short ...Golden Helix
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.
VarSeq 2.4.0: VSClinical ACMG Workflow from the User PerspectiveGolden Helix
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: VSClinical ACMG Workflow from the User PerspectiveGolden Helix
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 2.5.0: VSClinical AMP Workflow from the User PerspectiveGolden Helix
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.
Best Practices for Validating a Next-Gen Sequencing WorkflowGolden Helix
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.
VarSeq 2.4.0: Structural Variants and Advanced Automation in VSClinical ACMGGolden Helix
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.
AMP-Based Variant Classification with VSClinicalGolden Helix
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.
From Panels to Genomes with VarSeq: The Complete Tertiary Platform for Short ...Golden Helix
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.
VarSeq 2.4.0: VSClinical ACMG Workflow from the User PerspectiveGolden Helix
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: VSClinical ACMG Workflow from the User PerspectiveGolden Helix
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 2.5.0: VSClinical AMP Workflow from the User PerspectiveGolden Helix
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.
Best Practices for Validating a Next-Gen Sequencing WorkflowGolden Helix
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.
VarSeq 2.4.0: Structural Variants and Advanced Automation in VSClinical ACMGGolden Helix
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.
AMP-Based Variant Classification with VSClinicalGolden Helix
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.
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisGolden Helix
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.
Development of FDA MicroDB: A Regulatory-Grade Microbial Reference Databasenist-spin
"Development of FDA MicroDB: A Regulatory-Grade
Microbial Reference Database" presentation at the Standards for Pathogen Identification via NGS (SPIN) workshop hosted by National Institute for Standards and Technology October 2014 by Heike Sichtig, PhD from the FDA and Luke Tallon from IGS UMSOM.
Understanding and controlling for sample and platform biases in NGS assaysCandy Smellie
What is the impact of assay failure in your laboratory and how do you monitor for it?
The advancement of next-generation sequencing has provided invaluable resources to researchers in multiple industries and disciplines, and will be a major driver during the personalized medicine revolution that is upon us. However, while the cost of generating sequencing data continues to decrease this does not take into account the significant costs associated with the infrastructure and expertise that are required to develop a robust, routine NGS pipeline.
Specifically, as predicted by Sboner, et al in 2011, the cost of the sequencing portion of the experiment continues to decrease and the costs associated with upfront experimental design and downstream analysis dominate the cost of each assay. This is true whether you are performing a pre-clinical R&D project, and perhaps even more so for clinical assays. In the paper, the authors note the unpredictable and considerable ‘human time’ spent on the upstream design and downstream analysis. Here at Horizon, we aim to develop tools that help researchers and clinicians optimize these workflows to make NGS more reliable and ultimately, more affordable by streamlining these resource intensive areas.
Integrating Custom Gene Panels for Variant InnovationsGolden Helix
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.
Applied StemCell Inc’s MAPK genomic DNA (gDNA) reference standards represent biologically-relevant controls that can be directly incorporated into your sample processing workflows in order to optimize your protocols, evaluate assay sensitivity and specificity, and analyze the impact of workflow changes on downstream analysis. They represent ideal materials for both assay development and routine monitoring of assay performance.
The MAPK Genomic DNA Reference Standards are extracted from ASC’s panel of isogenic MAPK mutation cell lines with 50 recurrent pathway-activating mutations in the EGFR, KRAS and BRAF genes, based on data from the Sanger Institute’s COSMIC database.
Key Features of the MAPK Series gDNA Reference Standards:
Most comprehensive MAPK mutation panel on the market
Well-characterized colorectal cancer cells lines: EGFR (RKO), KRAS (RKO), BRAF (HCT116)
Paired, isogenic wild-type cell lines to serve as an ideal control
Footprint-free, homozygous mutations
Reference cell lines are expanded from single-cells, ensuring maximum homogeneity
Available in multiple formats, including slides, scrolls, and full FFPE blocks
Why Use Reference Materials (DNA: Reference standadrds provide a consistent and reliable resource for evaluating and optimizing various stages in your sample processing workflow. Whether you’re starting from DNA extraction, assay design, or library preparation, our reference materials can help you to identify and eliminate sources of variability within your protocols.
@AppliedStemCell offers validated, cellular reference standards for direct incorporation into sample processing workflows or quality control processes.
Highlights:
Overview of molecular reference materials
Workflow and QC for ONCOREF™ cell line generation (#CRISPR)
Advantages of CRISPR-engineered molecular reference standards
Applications of reference materials in assay development
Q & A
#sangersequencing #ngs
Development of FDA MicroDB: A Regulatory-Grade Microbial Reference DatabaseNathan Olson
"Development of FDA MicroDB: A Regulatory-Grade
Microbial Reference Database" presentation at the Standards for Pathogen Identification via NGS (SPIN) workshop hosted by the National Institute for Standards and Technology October 2014 by Heike Sichtig, PhD from the FDA and Luke Tallon from IGS UMSOM.
User perspective for somatic variant analysis in VSClinical AMPGolden Helix
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!
Maximizing the Benefits of Comprehensive Genomic Testing in Cancer Care with ...Golden Helix
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.
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...Golden Helix
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.
Presentation by Justin Zook at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on benchmarks for indels and structural variants.
Introducing VarSeq Dx as a Medical Device in the European UnionGolden Helix
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.
Introducing VSPGx: Pharmacogenomics Testing in VarSeqGolden Helix
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.
More Related Content
Similar to The Wide Spectrum of Next-Generation Sequencing Assays with VarSeq
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisGolden Helix
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.
Development of FDA MicroDB: A Regulatory-Grade Microbial Reference Databasenist-spin
"Development of FDA MicroDB: A Regulatory-Grade
Microbial Reference Database" presentation at the Standards for Pathogen Identification via NGS (SPIN) workshop hosted by National Institute for Standards and Technology October 2014 by Heike Sichtig, PhD from the FDA and Luke Tallon from IGS UMSOM.
Understanding and controlling for sample and platform biases in NGS assaysCandy Smellie
What is the impact of assay failure in your laboratory and how do you monitor for it?
The advancement of next-generation sequencing has provided invaluable resources to researchers in multiple industries and disciplines, and will be a major driver during the personalized medicine revolution that is upon us. However, while the cost of generating sequencing data continues to decrease this does not take into account the significant costs associated with the infrastructure and expertise that are required to develop a robust, routine NGS pipeline.
Specifically, as predicted by Sboner, et al in 2011, the cost of the sequencing portion of the experiment continues to decrease and the costs associated with upfront experimental design and downstream analysis dominate the cost of each assay. This is true whether you are performing a pre-clinical R&D project, and perhaps even more so for clinical assays. In the paper, the authors note the unpredictable and considerable ‘human time’ spent on the upstream design and downstream analysis. Here at Horizon, we aim to develop tools that help researchers and clinicians optimize these workflows to make NGS more reliable and ultimately, more affordable by streamlining these resource intensive areas.
Integrating Custom Gene Panels for Variant InnovationsGolden Helix
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.
Applied StemCell Inc’s MAPK genomic DNA (gDNA) reference standards represent biologically-relevant controls that can be directly incorporated into your sample processing workflows in order to optimize your protocols, evaluate assay sensitivity and specificity, and analyze the impact of workflow changes on downstream analysis. They represent ideal materials for both assay development and routine monitoring of assay performance.
The MAPK Genomic DNA Reference Standards are extracted from ASC’s panel of isogenic MAPK mutation cell lines with 50 recurrent pathway-activating mutations in the EGFR, KRAS and BRAF genes, based on data from the Sanger Institute’s COSMIC database.
Key Features of the MAPK Series gDNA Reference Standards:
Most comprehensive MAPK mutation panel on the market
Well-characterized colorectal cancer cells lines: EGFR (RKO), KRAS (RKO), BRAF (HCT116)
Paired, isogenic wild-type cell lines to serve as an ideal control
Footprint-free, homozygous mutations
Reference cell lines are expanded from single-cells, ensuring maximum homogeneity
Available in multiple formats, including slides, scrolls, and full FFPE blocks
Why Use Reference Materials (DNA: Reference standadrds provide a consistent and reliable resource for evaluating and optimizing various stages in your sample processing workflow. Whether you’re starting from DNA extraction, assay design, or library preparation, our reference materials can help you to identify and eliminate sources of variability within your protocols.
@AppliedStemCell offers validated, cellular reference standards for direct incorporation into sample processing workflows or quality control processes.
Highlights:
Overview of molecular reference materials
Workflow and QC for ONCOREF™ cell line generation (#CRISPR)
Advantages of CRISPR-engineered molecular reference standards
Applications of reference materials in assay development
Q & A
#sangersequencing #ngs
Development of FDA MicroDB: A Regulatory-Grade Microbial Reference DatabaseNathan Olson
"Development of FDA MicroDB: A Regulatory-Grade
Microbial Reference Database" presentation at the Standards for Pathogen Identification via NGS (SPIN) workshop hosted by the National Institute for Standards and Technology October 2014 by Heike Sichtig, PhD from the FDA and Luke Tallon from IGS UMSOM.
User perspective for somatic variant analysis in VSClinical AMPGolden Helix
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!
Maximizing the Benefits of Comprehensive Genomic Testing in Cancer Care with ...Golden Helix
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.
Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe D...Golden Helix
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.
Presentation by Justin Zook at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on benchmarks for indels and structural variants.
Similar to The Wide Spectrum of Next-Generation Sequencing Assays with VarSeq (20)
Introducing VarSeq Dx as a Medical Device in the European UnionGolden Helix
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.
Introducing VSPGx: Pharmacogenomics Testing in VarSeqGolden Helix
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.
Enhance Genomic Research with Polygenic Risk Score Calculations in SVSGolden Helix
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.
VarSeq 2.5.0: Empowering Family Planning through Carrier Screening AnalysisGolden Helix
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.
Identifying Oncogenic Variants in VarSeqGolden Helix
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
-How to evaluate the oncogenicity of a variant in VSClinical
Prenatal Genetic Screening with VarSeqGolden Helix
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.
Automated FASTQ to Reports with VarSeq Suite: A fast, flexible solutionGolden Helix
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.
A User’s Perspective: Somatic Variant Analysis in VarSeq 2.3.0Golden Helix
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
VarSeq 2.3.0: Supporting the Full Spectrum of Genomic VariationGolden Helix
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
VarSeq 2.3.0: New TSO-500 and Genomic Signature Support in VSClinical AMPGolden Helix
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.
Single Sample and Family Based Genome Analysis With VarSeqGolden Helix
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 LabGolden Helix
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 VarSeqGolden Helix
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 WorkflowsGolden Helix
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.
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 SuiteGolden Helix
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.
Golden Helix’s SNP & Variation Suite (SVS) has been used by researchers around the world to do association testing and trait analysis on large cohorts of samples in both humans and other species. As samples size increase to do population-scale genomics, the analysis methods need to adapt to remain computable on your analysis workstation.
One of the most popular methods for determining population structure in SVS is Principal Component Analysis. In this webcast, we review the fundamentals of this methodology, as well as how we have advanced the state of the art by implementing a new “Large Data PCA” capability in SVS, handling over 10 times as many samples as previously possible at a fraction of the time. Join us as we cover:
A review of SVS association testing and trait analysis capabilities
Usage of Principle Component Analysis to discern population structure
Scaling PCA beyond the limitations of computer hardware Other SVS improvements based on ongoing feedback from the user community
SVS continues to move forward as a flexible and powerful tool to perform genotype and Large-N variant analysis. We hope you enjoy this webcast highlighting the exciting new features and select enhancements we have made.
Using Golden Helix CancerKB to Accelerate NGS Cancer TestingGolden Helix
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
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
How to Give Better Lectures: Some Tips for Doctors
The Wide Spectrum of Next-Generation Sequencing Assays with VarSeq
1. The Wide Spectrum of Next-Generation
Sequencing Assays with VarSeq
April 19, 2023
Presented by Darby Kammeraad, Director of Field Application Services, and
Jennifer Dankoff, PhD, Field Application Scientist
3. The Wide Spectrum of Next-Generation
Sequencing Assays with VarSeq
April 19, 2023
Presented by Darby Kammeraad, Director of Field Application Services, and
Jennifer Dankoff, PhD, Field Application Scientist
4. NIH Grant Funding Acknowledgments
4
• Research reported in this publication was supported by the National Institute Of General Medical Sciences of
the National Institutes of Health under:
o Award Number R43GM128485-01
o Award Number R43GM128485-02
o Award Number 2R44 GM125432-01
o Award Number 2R44 GM125432-02
o Montana SMIR/STTR Matching Funds Program Grant Agreement Number 19-51-RCSBIR-005
• PI is Dr. Andreas Scherer, CEO of 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.
5. Who Are We?
5
Golden Helix is a global bioinformatics company founded in 1998
Filtering and Annotation
ACMG & AMP Guidelines
Clinical Reports
CNV Analysis
CNV Analysis
GWAS | Genomic Prediction
Large-N Population Studies
RNA-Seq
Large-N CNV-Analysis
Variant Warehouse
Centralized Annotations
Hosted Reports
Sharing and Integration
Pipeline: Run Workflows
8. The Golden Helix Difference
8
FLEXIBLE DEPLOYMENT
On premise or in a private
cloud
BUSINESS MODEL
Annual fee for software,
training and support
CLIENT CENTRIC
Unlimited support from the
very beginning
SINGLE SOLUTION
Comprehensive cancer and
germline diagnostics
SCALABILITY
Gene panels to whole
exomes or genomes
THROUGHPUT
Automated pipeline
capabilities
QUALITY
Clinical reports correct the
first time
11. Constructing a Panel:
Traditional Approach
11
• Targeted NGS panels lead to highly
specific results.
o I.e., pathogenic variants in BRCA1 and
BRCA2.
• Filter chains are simplistic and
streamlined.
• Workflow templates can be
reapplied to new samples.
• The turn around time to report is
expedited with prerendered
interpretations from CancerKB for
somatic analysis.
Pro:
Design of primer kit is nowadays simple
Efficient secondary and tertiary: high sample turnover
Con:
Difficult to modify panel; have to rebuild the kit.
Always limited to scope of panel for genomic findings
1. Curate list of
genes
Version 1
Breast Cancer
BRCA1, BRCA2
2. Submit
to primer
company
3.
Sequence
with
custom kit
4. 2’:
FASTQ ->
BAM/VCF
5. 3’
analysis:
isolate
relevant
variant
6. Report on
findings:
BRCA2
LOF: Y1739*
Market demands:
need for updated
panel and more
extensive report!!
Version 2:
Updated Breast
Cancer Panel
BRCA1, BRCA2, ATM,
CHEK2, PALB2
12. Virtual Panel,
the Modern Approach
12
• Time saving: No need to design specific panels
prior to sequencing.
• Retroactively apply specific phenotypic searches
or panels to WES.
o High reengineering potential to suit current workflow
needs.
• Cost saving and gains: Reimbursement for the
lab when utilizing specific genetic searches.
• Reporting: Flexible report templates can be
applied to a multitude of panels.
• Automation: FASTQ to reporting with VSPipeline.
Full Panel Subpanel
General cardio panel:
2,563 genes
ACTN2, DES, NDUFA9…
Dilated cardiomyopathy:
170 genes
ACTN2, DES, CHKB…
Hypertrophic cardiomyopathy:
280 genes
CAV1, NDUFA9, FOS…
Hearing impairment:
2,226 genes
GIPC1, FGFR2, PRPF3…
Hearing loss:
409 genes
ABHD12, ACTG1, ADGRV1…
Usher syndrome:
83 genes
DHDDS, POMGNT1, RPE65…
Intellectual disability (ID):
3,713 genes
TOR1A, POLA1, TMCO1…
Autism:
735 genes
ADNP, ANK2, DSCAM…
Neurodevelopmental delay:
2,189 genes
TOR1A, POLA1, MID1…
Pro:
• Large scale data expands yield on relevant variants
• Retroactively apply gene searches
• Eliminates need to reorder new panel kits
Con:
• User must validate the virtual panels (ACMG guidelines)
• Construction of panel in tertiary phase
Table based on ACMG guidelines for panel construction:
https://doi.org/10.1038/s41436-019-0666-z
13. TSO500 somatic panel
13
• Samples: Applicable to liquid biopsies, formalin-
fixed paraffin embedded tissue samples (FFPE), and
more.
• Variants: SNVs, CNVs, structural variants, and
fusions.
• Import: Comprehensive genomic profiling (TSO500,
IonTorrent, Archer Fusions, and more)
• Comprehensive interpretation: CancerKB has
clinical interpretations scoped for TSO500, ready to
supplement biomarker reporting.
• Reporting: Flexible templates offer complete and
customizable clinical reports.
• Automation: VSPipeline can take the FASTQ all the
way to clinical report, ready for clinician approval.
TMB: High
MSI: High
BRCA2
LOF: Y1739*
Olaparib
& Talazoparib
tosylate
Cancer
specific
workflow
• Cancer Panels
• CIViC
• DrugBank
Demonstration
example:
CancerKB
• Drug recommendations
• Complete interpretations
• 500+ interpretations from
cancer experts
Final
reporting
• Lab director sign off
• Flexible report templates
• Total customization
Scripts
bring in
biomarkers
• Genomic Signatures
• Negative Findings
• Immunotherapy biomarkers
• Clinical Trails
Sample
sequencing
• Solid tumor sequencing
• Liquid biopsy
• FFPE tissue samples
14. Hereditary Trio Screening
14
• Sophisticated filtering potential on inheritance
models (de novo, dominant het, recessive, etc)
o Trio template with inheritance models pre-built and
ready with install.
• Variant prioritization: Through Virtual Panels or
Phenotypic based (PhoRank) prioritization
o Examples: developmental delay, early onset
disorders, auto-immune conditions, etc..
• Variants: SNVs, Indels, and CNVs
o Capture potential large aneuploidy events (ex.
Trisomy 21) down to single nucleotide changes
• Reporting: Trio based clinical report shipped with
VarSeq and ready for use.
Pro:
• Determine heritability of variant and verify kinship
• Assess carrier risks for parents for future offspring
Con:
• Need to run more samples at higher cost
• Increase computation/analysis time with higher sample load
De novo
Recessive
homozygous
Dominant
heterozygous
Compound
heterozygous
X-Linked
Inheritance Models
Prenatal
screening to
find risk alleles
Example
• PAH gene
• LOF
• Phenotype: Phenylketonuria
• Classification: Pathogenic
15. Singleton Workflows:
Whole Exome Sequencing
15
• Time saving: No need to design specific panels
prior to sequencing.
• Variant prioritization: Through Virtual Panels or
Phenotypic based (PhoRank) prioritization
o Examples: developmental delay, early onset
disorders, auto-immune conditions, etc..
• Cost saving and gains: Reimbursement for the
lab when utilizing specific genetic searches.
o Avoid unnecessary sample sequencing.
• Reporting: Various templates available for
general Mendelian or panel specific reporting.
Pro:
• No need to run more samples at higher cost
• Decrease computation/analysis time with higher sample load
Con (if applicable):
• Difficult to differentiate maternal and paternal contributions
without longread technology.
Prenatal
screening of
single sample
Standard
filtering
workflow
• Quality (DP, GQ, VAF, ...)
• Pop Freq (gnomAD, 1kg, …)
• Ontology (LOF, missense,
splice)
Diagnosis
or risk
analysis
• PhoRank phenotypes
• Virtual panels
Example
• PAH gene
• LOF
• Phenotype: Phenylketonuria
• Classification: Pathogenic
16. Whole Genome Sequencing:
Ultimate Diagnostic Yield
16
• Cost: The cost of WGS is dropping.
o Like with virtual panels, reimbursement is
possible with specific assays.
• Flexibility: There is a wide breadth of
assays possible.
o Design and utilize standard diagnostic
workflows
o Additional design for incidental findings or
risk analysis.
o Population level analysis
• Intronic searches: The sequencing
method that will allow for deep intronic
variant searches.
• Leverage population frequency data
with VSWarehouse.
Pro:
• Start from large scale data and narrow scope
• Greatly expands diagnostic yield for clinically relevant variants not detected via exome
Con
• Ideally run on server to tackle larger computational process of genomes
Example:
Deep
Intronic
• MSH2 gene
• Novel splice donor site
• Disorder: Lynch syndrome
• Classification: Pathogenic
17. Project Examples
17
Panels
• Traditional BRCA1/2 Panel
• Applying Virtual Panel for hereditary breast carcinoma
• TSO500 somatic workflow
Exome
• Hereditary Trio: LOF variant in PAH gene
• Singleton analysis: LOF variant in PAH gene
Genome
• Genome Wide Assay: Deep intronic MSH2 basechange
introducing novel splice site
19. Summary Slide
• Golden Helix software scales from gene panel to genomes.
• Support of various variant types.
• Utilization of both virtual panels and phenotypic prioritization with PhoRank.
• Streamlined somatic analysis for TSO500 and more.
o AMP evaluation in VSClinical paired with professionally curated interpretations/treatments via CancerKB.
• All workflows highly automatable with VSPipeline.
o FASTQ to finished project or report.
• The cohort of genomic data is stored and leveraged via VSWarehouse.
• Unlimited support and training with the Golden Helix FAS Team.
19
20. NIH Grant Funding Acknowledgments
20
• Research reported in this publication was supported by the National Institute Of General Medical Sciences of
the National Institutes of Health under:
o Award Number R43GM128485-01
o Award Number R43GM128485-02
o Award Number 2R44 GM125432-01
o Award Number 2R44 GM125432-02
o Montana SMIR/STTR Matching Funds Program Grant Agreement Number 19-51-RCSBIR-005
• PI is Dr. Andreas Scherer, CEO of 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. 25 Licenses for 25 Months
22
Celebrating 25 Years in Business
• Limited quantity
• Licenses are 25-month license periods
• Available to new customers only
• Orders must be received by June 15, 2023
• Visit goldenhelix.com/forms/25-for-25 or
scan the QR code below
23. Conferences
23
Bio-IT World Conference, Boston
• May 16 – 18, 2023
• Andreas Scherer, CEO, presenting: Achieving Economic Success as an
NGS Labs: Strategy and Implementation
European Human Genetics Conference, Booth #566
• June 10 – 13, 2023
• Glasgow, UK
AMP Europe, Milan, Italy
• June 18 – 20, 2023
• Milan, Italy
Before we start diving into the subject, I wanted mention our appreciation for our grant funding from NIH.
The research reported in this publication was supported by the National institute of general medical sciences of the national institutes of health under the listed awards.
We are also grateful to have received local grant funding from the state of Montana.
Our PI is Dr. Andreas Scherer who is also the CEO at Golden Helix and the content described today is the responsibility of the authors and does not officially represent the views of the NIH.
So with that covered, lets take just a few minutes to talk a little bit about our company Golden Helix.
Golden Helix is a global bioinformatics software and analytics company that enables research and clinical practices to analyze large genomic datasets.
We were originally founded in 1998 based off pharmacogenomics work performed at GlaxoSmithKline, who is still a primary investor in our company.
VarSeq is our flagship product and serves as a clinical tertiary analysis tool. At its core, it is a variant annotation and filtration engine.
But also gives users ability to automate the AMP or ACMG variant guidelines.
VarSeq also has the capability to detect copy number variations scaling from single exome to large aneuploidy events.
Lastly, the finalization of variant interpretation and classification is further optimized with the VarSeq clinical reporting capability.
Users can integrate all of these features into a standardized workflow, save as a template, and automated the major of this tertiary process with our Vspipeline tool
Paired with VarSeq is VSWarehouse which serves as a locally installed repository for the large amount of useful genomic data collected from your samples.
Warehouse not only solves the issue of private data storage for ever-increasing genomic content, but also is fully queryable and auditable and allows for the definability of user access for project managers or collaborators.
Lastly, our research platform, SVS, enables researchers to perform complex analysis and visualizations on genomic and phenotypic data. SVS has a range of tools to perform GWAW, genomic prediction, and RNA-Seq analysis, among other common research applications.
Over the course of 20 years, Our software has been very well received by the industry. We have been cited in thousands of peer-reviewed publications in reputable journals, as one testament to our customer base.
We work with over 400 organizations all over the globe. This includes top-tier institutions, like Stanford and yale, government organizations like the NCI and NIH, clinics such as Sick Kids, and many other genetic testing labs.
We now have well over 20,000 installs of our products and with 1,000’s of unique users.
So how is this relevant to you?
At Golden Helix, we strive to be the complete solution for our customers which is defined across seven pillars comprising the Golden Helix difference.
Golden Helix offers a single software solution that encompasses germline, somatic, and CNV analysis.
Our software is also highly scalable, supporting gene panel to whole genome sequencing workflows.
With our complete automation capabilities, we now offer a FASTQ or VCF to report pipeline.
Our software is locally deployed, or installed in cloud, respecting our customers data privacy
Our business model of annual subscription per user means you are able to increase your workload without increasing analysis fees.
And the license comes with unlimited training and support from our FAS team to facilitate Customer Success.
So now that we’ve talked a bit about the value of Golden Helix as a company, lets switch to the topic of todays discussion and cover the versatility of NGS workflow design with VarSeq
JEN: Thank you Darby, I’m happy to be here!
J: Before we head into a few project demonstrations, let’s discuss the logic surrounding VarSeq and VSClinical. VarSeq and VSClinical leverage ACMG and AMP guidelines to determine pathogenicity or oncogenicity for both small variants and copy number variants.
There is a lot to consider when reviewing all the components for the ACMG or AMP guidelines manually, which makes all the hard work in automating this process so valuable. In its most basic form, VarSeq can be seen as a three stage process. We have Stage one, which encompasses the importing, detection, and filtering of variants from your VCF file. All the imported or detected variants pass through a user define template that is based on a variety of public databases and algorithms. Today we will see how this is applicable to small gene panels all the way to whole genome projects.
After isolating our germline SNVs, INDELs, or CNVs of interest, these will be carried into stage 2 of the analysis, where they will be analyzed in VSClinical through a review of the ACMG or AMP guidelines.
Following the variant evaluation, we are able to render the final interpretation results in a complete clinical report which is the third and final stage of analysis. The overarching steps described here can now be applied to any of the workflows we will be getting into, and these will range in complexity from a very small gene panel to whole genome workflows. So let’s take a look at how a panel is traditionally constructed, along with the upsides and downsides to this process.
**NEXT SLIDE**
Most of us here are familiar with the process behind constructing a sequencing kit for small panels, if not still using this method. This method does have some advantages, for example, companies make the design of the primer kits simple and straightforward. Additionally, this route of analysis is fairly efficient when looking at simple panels, maybe only a few genes, especially in a situation where a lab has high sample turn over for a limited number of panels. Let’s take a look at this process. First, I know which genes I want ahead of time, and have submitted those to the primer company. After receiving my kit, I will sequence my samples, then I will go through the secondary analysis, converting my FASTQs to BAMs and VCFs. After that is the matter of applying a simple filtering strategy to isolate my variants of interest, and then reporting on my clinical findings.
Our targeted NGS panel is going to lead to highly specific results, and the workflow template can be applied to this panel over and over again. Here we are going to use a BRCA1, BRCA2 panel, resulting in a loss of function variant in BRCA2. Our path to reporting is expedited, as we can supplement our report with prerendered interpretations from our CancerKB database.
Now, the problems here become obvious when we look at changes in the market demands. **CLICK** For example, the need to update the gene panel for a more extensive report. Here, that would be if I wanted to report on additional genes such as ATM, CHEK2, and PALB2 in addition to BRCA1 and BRCA2. Changing the panel at this point means the clinician will have to go back to version one, redesigning and resubmitting a gene list to a company. With this method, you are limited to the scope of the panel for genomic findings. If we want to increase our flexibility for reporting, it would make sense to begin with sequencing the exome if not genome to maximize potential on diagnostic yield for ever expanding panels and apply them virtually rather than go through a limited sequencing kit.
A good example here would be transitioning to an exome level data set, where you can redesign your panels easily by applying virtual panels. With this model, we would version those panels for use in audits. Applying virtual panels can save time in the long run as there is no need to design specific panels prior to sequencing. The ability to retroactively apply phenotypic searches or gene panels to Whole exome sequencing level data gives an enormous reengineering potential that can lead to specific insurance reimbursements. Moreover, when it comes to reporting, VSClinical has a number of predesigned report templates that can easily be applied to numerous assay designs. The ability to automate this process, going from FASTQ to reporting with VSPipeline can also expedite sample turn over in the lab.
Now, this panel construction can seem daunting, but there are guidelines from the ACMG group that can take you through this process. Here, we are looking at several examples of broad disorder panels with the number of genes in each panel, along with more specific subpanels and their respective number of genes. I also have a link to the ACMG guidelines paper that gives details for these panel constructions. The idea is, by starting at whole exome sequencing, we do not have to start at one kit, for example, dilated cardiomyopathy, and then start over with a new kit if the phenotype is revised to hyper-tro-phic cardiomyopathy. I simply have to apply the new virtual panel to the data set. VarSeq has the tools to make this process simple, including the Gene Panel Manager that we will take a look at in our demonstration. These tools make constructing panels as easy as possible.
Overall, the pros with applying virtual panels include the ability to expand on diagnostic yield, while remaining adaptive for all potential reimbursement and reporting for evolving panels.
The cons are, obviously, the construction of the panels themselves, but there are tools and guidelines to help you in this process.
The ease of use of panels to reporting is best exemplified with our support of TSO500 somatic analysis.
In addition to the construction of virtual gene panels, I wanted to highlight to our viewers, the streamlined integration of our TSO500 workflows with comprehensive genomic profiling. Starting from the sequencing stage, VarSeq analysis is agnostic as to the origin of the somatic data, as long as that data is in a standard format. This means we can cover solid tumor sequencing, liquid biopsies, FFPE tissue samples, and more all under the same workflow umbrella. The variants supported for analysis include SNV, CNVs, structural variants, and fusions.
The workflow, starting with panels, then virtual panels, and now our TSO500 somatic panel, has been getting gradually more involved. As we become tumor type specific, we are going to bring in more cancer elements, such as specific cancer sub-panels, or cancer annotation sources like CIViC and DrugBank. Moving into VSClinical, you will see that our comprehensive genomic profiling will bring in additional fields, like genomic signatures, TMB, MSI, or HRD. We will bring in negative findings that are specific to tumor types. We will also bring in immunotherapy biomarkers and relevant clinical trials.
This comprehensive overview is enhanced by our inhouse Cancer Knowledgebase. CancerKB has prerendered clinical interpretations scoped for TSO500, and is ready to supplement biomarker reporting.
Last, we have our automation component, where with VSPipeline, we can go all the way from FASTQ to clinical report, ready for a lab director sign off. The large amount of information available truly makes the TSO500 somatic panel with VarSeq the comprehensive somatic analysis.
Now that we have covered our somatic panels, we are going to pivot, and I am going to hand things back to Darby to tell us about working with whole exome, germline workflows.
FFPE- formalin fixed paraffin embedded tissue samples
CGP- comprehensive genomic profiling
TMB, MSI, HRD
Thank you Jen for breaking down the evolution of the gene panel and what tools we have to simplify somatic analysis. Switching to the germline topic, an example of a typical exome analysis would be Trio or family based analysis, for two parents and any number of probands. From a workflow perspective, this is relatively sophisticated when designing filters that account for different inheritance models. The inheritance model strategy can also be utilized with VarSeq called CNVs as well. One common hurdle with large scale data, like the exome in a clinical space, is that each patient brings with them a unique phenotype or diagnosis. Because of this, panels can be difficult to construct for each unique case. The solution is implementing GHI’s PhoRank algorithm that allows users to prioritize variants that are in genes highly associated with the diagnosed phenotype. This helps users overcome the required adaptation to running larger scale data. When doing the variant evaluation, VSClinical accounts for inheritance based ACMG criteria for the clinically relevant variants. Just as is the case with panels, this process is highly automatable. One drawback to consider with ‘trios’ is the increased costs for each sample of the family, and increased analytical time. It is for this reason that we wanted to show you how you can reach the same outcome with a singleton analysis rather than run the trio.
So the outcome is potentially similar to that of the trio analysis but the upside for the single sample workflow is efficiency, reduced cost and overall simplicity. The filter chain will be a bit different as we let go of the possible inheritance models, but you’ll see in the demo there are a number of creative ways to still reduce the number of variants you need to evaluate. One thing to consider is the con of switching to single sample from trios, you lose the ability to run any additional risk analysis on the parents if they seek to have other offspring. However, as you saw in the slide before, if the risk analysis is needed, the trio template is available and ready to be applied for our users workflows. Additionally, you’ll see in our trio example the context of variants that are in the cis and trans state can affect relevant classification criteria and one thing that will assist here in the near future is the phased genotypes with long read technology if limiting your analysis to just the proband. This is all in the context of the exome, but we still might consider running the genome as it provides the ultimate diagnostic yield.
Here is an example of the coverage from a genome on top compared to the targeted exome coverage just underneath. The depth of coverage for the exome looks quite nice and any allele in the exon or perhaps just on the edge near a canonical splice site would be identifiable. However there are severe limits, and I created an example to purposefully demonstrate the inability for the exome to capture a deep intronic pathogenic allele that no clinical lab would want to miss. This is the diagnostic power and value of the genome, as it will have the adequate coverage necessary to detect alleles like our example MHS2 novel splice variant that is well known pathogenic. So obviously genomes come at a cost for computation burden but our tools support the transition to genomes as they become more common due to reduced cost and want to assess population level genetic findings for various populations. Not only do our users have the ability to streamline the process of genomes with tools like VS pipeline on your server but we also support CRAM files now to tackle the data storage issue that comes with reviewing coverage at a genome level. Now that we’ve covered some workflow and data scale highlights, lets review our example variants for the software demonstration
So we have covered a lot of great highlights concerning the evolution of NGS assays and our demonstration is going to give examples moving from the panel to genome level analysis.
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And now onto our product demonstration~
In summary, we are trying to facilitate the evolution of NGS assays with the goal of standardizing the exome and the genome. We do this while supporting the different variant types such as SNVs, INDELs, CNVs, and fusions. When panels fall short, users can rely on a phenotypic based variant prioritization with the PhoRank algorithm. Additionally, we aim to expedite the somatic review with our AMP evaluation tool in VSClinical paired with CancerKB, with a minimal standard held against the TSO500 gene list. In any scenario, be it panels, exome, genome, germline or somatic, all workflows are highly automatable, to save the user time and cost. With assay design in Golden Helix software, comes limitless training with our FAS team.
Before we start diving into the subject, I wanted mention our appreciation for our grant funding from NIH.
The research reported in this publication was supported by the National institute of general medical sciences of the national institutes of health under the listed awards.
We are also grateful to have received local grant funding from the state of Montana. Our PI is Dr. Andreas Scherer who is also the CEO at Golden Helix and the content described today is the responsibility of the authors and does not officially represent the views of the NIH.
So with that covered, lets take just a few minutes to talk a little bit about our company Golden Helix.
Again, I want to mention how grateful we are we are thankful of grants such as this which support the advancement and development of our software to create the high quality software you'll see today.
So with that covered, lets take a few minutes to talk a little bit about our company Golden Helix.