November 4, 2020
Golden Helix has been in close communication with the publishers of the ACMG guidelines and the ClinGen group to receive expert advice on how to interpret CNVs called on NGS data. These guidelines provide a robust set of rules for interpreting intragenic deletions and duplications, which is summarized into an intricate decision tree that is broken down into 80 distinct criteria. This complexity is further compounded by many important caveats, exceptions, and considerations known to many in the CNV clinical workspace but are not mentioned in the published guidelines...
October 14, 2020
As CNV detection has become widely adopted as a component of NGS testing, the demand has grown for an interpreting framework specific to CNVs in the context of rare and inherited disorders. Earlier this year, a ClinGen working group in collaboration with ACMG, published new guidelines for the interpreting and reporting of CNVs detected by NGS...
September 9, 2020
As CNV detection has become widely adopted as a component of NGS testing, the demand has grown for an interpreting framework specific to CNVs in the context of rare and inherited disorders. Earlier this year, a ClinGen working group in collaboration with ACMG, published new guidelines for the interpreting and reporting of CNVs detected by NGS. We at Golden Helix have been hard at work expanding VSClinical to incorporate these new scoring and evaluation criteria for the interpretation and clinical reporting of CNVs alongside small variants in our popular guided workflow for following the ACMG guidelines...
August 12, 2020
VarSeq is a tertiary analysis platform that allows users to filter and annotate NGS sequencing data to identify clinically relevant variants. Following this workflow, VSClinical can then be used to automate both germline and somatic variant analysis in accordance with the ACMG and AMP guidelines by using a variety of functional prediction models and clinical and reviewer-based annotations...
July 15, 2020
Golden Helix’s SNP & Variation Suite (SVS) has been used by researchers around the world to do trait analysis and association testing on large cohorts of samples in both humans and other species. As Next-Generation Sequencing of whole genomes becomes more affordable, large cohorts of Whole Genome Sequencing (WGS) samples are available to search for additional trait association signals that were not found in array-based testing...
June 10, 2020
Many of the criteria above are shared by the ACMG Guidelines for germline variant interpretation, such as population frequency information, variant effect on protein function, and nearby pathogenic variants in catalogs such as ClinVar. However, other criteria are specific to the world of somatic variant interpretation...
Yearly Clinical Review of a Patient’s WGS Results Leads to a New Gene Candidate for a Complex Cardiomyopathy Phenotype
May 27, 2020
The rapid evolution of genetic disease understanding and expanding genetic databases behooves clinician specialists to regularly review the status of clinical genetic test panels, reevaluating the status of identified variants. With the increasing use of WES and WGS sequencing, these results likely also need regular review...
May 6, 2020
The COVID-19 outbreak is an unprecedented event in terms of its impact on public health and the global economy. While we may see the development of an immunization strategy as the ultimate solution, sequencing the virus with Next-Generation Sequencing (NGS) provides useful diagnostic and research findings to impact the course of this pandemic. As a provider of NGS analysis solutions spanning clinical and research capabilities, Golden Helix has a number of analytical solutions relevant to these different use cases for the analysis of the SARS-CoV-2 virus...
April 22, 2020
Approximately 8 million Americans suffer yearly from interstitial cystitis, a chronic bladder inflammatory condition; 80% of these sufferers are women (ICA 2017). About 12.2 women in the United States experience vaginal and bladder infections yearly (NIDDKD 2011). And 65% of the 35.2 million who endure irritable bowel syndrome are also women (Canaban+, 2014)...
April 8, 2020
Golden Helix ships a variety of templates that are designed to provide a starting point for users to evaluate variants in VarSeq. Naturally, as users become more familiar with the software, there is a desire and necessity to tailor the template design to accommodate a more thorough variant analysis. To add to these template customizations there are several algorithms and annotation sources available in VarSeq that many users may not know of...
March 25, 2020
Heat stress is a major limiting factor of beef cattle production. Over 40% of the world’s beef cattle reside in tropical or subtropical climates known for their hot and humid conditions. When cattle experience heat stress they exhibit lower feed intake, reduced pregnancy rates and in extreme cases even death. In the U.S. alone, heat stress results in a loss of $369 million a year due to reduced animal performance...
March 4, 2020
Golden Helix software solutions provide many automated services to streamline variant analysis. This is true when regarding the curation of critical annotations, automation of tertiary project processing via VSPipeline, and of course, the automation of the ACMG and AMP guidelines. Our first iteration when integrating the AMP/ASCO guidelines has added dramatic simplicity...
February 12, 2020
When interpreting a variant using the AMP/ASCO guidelines for somatic variant interpretation, clinicians must determine whether the variant can be considered a biomarker that affects clinical care by predicting sensitivity, resistance, or toxicity to a specific therapy. Such a determination requires the investigation of multiple evidence sources, including clinical trials, FDA approved therapies and peer-reviewed studies...
January 15, 2020
Genetic testing labs deal with personal data in categories with the highest level of security requirements: personal identity and medical records. Given the liability and risk associated with a breach of this secure information, it is not surprising that many labs and institutes that aggregate genomic data prefer if not require on-premise analysis and storage solutions...
December 4, 2019
GWAS is a powerful approach to identify genomic regions and genetic variants associated with phenotypes. Whether you are investigating alleles that are common in humans with disease or finding single nucleotide variations that are optimal for cattle breeding, for whatever desirable trait you may be searching for, it is important to analyze SNPs to explain the variation that exists within that trait...
November 6, 2019
Delve into VSWarehouse with a focus on our new capability of storing somatic variant projects and catalogs built for the AMP Guidelines within VSClinical. We also demonstrate how VSWarehouse efficiently navigates through stored variants via the VSWarehouse Browser...
Clinical Variant Analysis with VSClinical: Virtus Diagnostics Case Study and Review of ACMG & AMP Guidelines
October 30, 2019
Val Hyland and Peter Field from Virtus Diagnostics (Brisbane) discuss two cases from their cohort of 1095 patients that were screened for inherited diseases using the Illumina 552 genes Inherited Disease screening panel. They found 637 different pathogenic/likely pathogenic variants in 252 genes using a combination of software tools from Golden Helix, including VSClinical, Sentieon and Illumina. This presentation is based on a poster first presented at the HGSA Wellington Conference in 2019...
October 9, 2019
The common approaches to detecting copy number variants (CNVs) are chromosomal microarray and MLPA. However, both options increase analysis time, per sample costs, and are limited to the size of CNV events that can be detected. VarSeq’s CNV caller, on the other hand, allows users to detect CNVs from the coverage profile stored in the BAM file, which allows you to utilize your existing NGS data and perform the analysis all in one suite. Coupled with this innovative feature is the ability to annotate CNV events against a variety of databases, and by incorporating our VSClinical AMP workflow, we can now assess CNVs as potential biomarkers...
September 11, 2019
Interpreting somatic variants for the clinical genetic testing of tumors requires hands-on time of the most skilled clinical lab personnel. Various clinical and genomic sources must be queried, papers and guidelines referenced, and an evaluation of the clinical actionability of the mutation determined by the following the AMP guidelines. Yet, there is tremendous potential for reuse of this time consuming and valuable work...
August 7, 2019
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...
GWAS to Identify Genetics that Influence Calf Health from Holstein and Crossbred Dairy Cows and Calves
July 24, 2019
Genome-wide association analysis is a powerful tool for explaining the phenotypic effects of dairy cattle on the genome and knowledge of genes associated with dairy cattle phenotypes. SNP & Variation Suite (SVS) has assisted the University of Minnesota, West Central Research and Outreach Center to determine the association of genetics groups with calf and cow health. These results are used to improve selection indexes for genomic evaluations for dairy cattle and will help improve the profitability of dairy production systems...
July 10, 2019
Before accessing the clinical evidence associated with a specific variation, one must establish that the variant is likely to be a driver mutation, which generates functional changes that enhance tumor cell proliferation. In this webcast, we will discuss VSClinical’s capabilities for determining 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...
June 12, 2019
The individualized nature of tumors requires genomic testing for providing the best outcomes for patients. Next Generation Sequencing enables the detection of small mutations, copy number changes, and common fusions affordably and with high precision. However, the interpretation of these detected variants is arduous without a comprehensive analytical workflow that can incorporate all the bioinformatic and clinical evidence involved in following the AMP guidelines for the scoring and reporting of somatic mutations...
May 29, 2019
Since the development of our NGS-based CNV solutions for VarSeq and SVS, we've generated a long list of content demonstrating simple workflows to help isolate clinically relevant events for a given sample. However, it's just as important to talk about the exclusionary filters that help remove any extraneous CNVs from the analysis...
May 8, 2019
Anyone handling NGS data understands the constant issue of not only storing all the variant data but also the difficulties in querying through a massive dataset. VarSeq has grown an excellent reputation for being a powerful filtration and annotation engine for NGS data. Tightly coupled with VarSeq is our genomic repository solution, VSWarehouse. VSWarehouse provides a means of storing all variant cohort data as well as rapid querying capabilities to quickly navigate through the, potentially, millions of variants you may amass over time...
April 24, 2019
Despite the great advances achieved in clinical genetics thanks to the incorporation of NGS (Next Generation Sequencing), a significant percentage of patients with diseases of genetic origin still do not have a conclusive molecular diagnosis. The incorporation of state-of-the-art bioinformatic methods has allowed the implementation of CNVs (Copy Number Variants) detection in NGS analysis, improving its diagnostic efficiency. In this study, the clinical utility of the detection of CNVs by NGS has been proven...
Enabling research translation: generating clinical genetic reports to improve the management of cardiovascular disease
April 10, 2019
Heart disease is a leading cause of death and disability in Canada and worldwide, which largely results from the insidious process not being identified or treated until it is too late (1). This is best exemplified by patients with familial hypercholesterolemia (FH). FH is the most common autosomal dominant genetic disorder resulting from pathogenic genetic variants in the LDLR, APOB, and/or PCSK9 genes (~1 out of 225 people) (2). These genetic variants cause elevated low-density lipoprotein cholesterol, more commonly known as “bad cholesterol”, and significantly increase these patients’ risk of cardiovascular disease...
March 27, 2019
Evaluating variants according to the ACMG guidelines can be an extensive process as it requires an in-depth understanding of all available criteria for any variant. Even the most adept clinicians familiar to the guidelines suffer from this tedious manual process and from the challenge of teaching these fundamentals to new technicians. VSClinical is an automated solution to the complex ACMG guidelines process. In this webcast, we will present how VSClinical follows the true-to-form ACMG classification ...
March 13, 2019
In a clinical setting, investing in automatable workflows provides two pay-backs: First, less time is spent by the constraint resource of laboratory staff and medical professionals. Second, and more importantly, the possibilities for errors is reduced. In this webcast, we will cover the full analysis workflow from sequencer to clinical report and how each component can be automated with the Golden Helix clinical stack...
February 13, 2019
To adequately assess a variant's pathogenicity it is crucial to take into account the variant's effect on splicing. While mutations that disrupt the pairs of bases at the beginning of a splice site are straightforward to identify, detection of disrupted splice sites caused by changes to the splice motif is more difficult. In this webcast, we will discuss VarSeq's capabilities for...
January 9, 2019
With Next-Gen Sequencing becoming a routine method of rapidly investigating cancer mutations, having access to accurate and large somatic variant catalogs is paramount. We at Golden Helix are excited to announce our newly released COSMIC 87 track. This updated version of the world's largest and most comprehensive somatic track provides a number of significant improvements.
December 5, 2018
Copy number variation (CNV) can be drivers in many genetic diseases and can be called using our clinical and research application platforms: VarSeq and SVS, respectively. Using these platforms, CNV are called using the existing coverage data stored in your BAM files and are detected using a targeted or binned region approach. As the targeted approach has been demonstrated in previous webcasts, we wanted to focus on the binned region approach that is implemented for detecting CNV from shallow-coverage whole genome sequencing (WGS) data.
November 7, 2018
Earlier this year we launched our latest product VSClinical featuring workflow support for the ACMG guidelines with advanced automation capabilities and per-criteria recommendations. It has been amazing to watch the adoption of this product in labs doing both germline and in some cases cancer variant interpretation. Our latest VarSeq 2.1 release demonstrates our approach to iterative product improvements based on our engaged relationship with our customers and includes numerous improvements...
October 24, 2018
We will be showing users the process of annotating and filtering CNVs in VarSeq. This will include a discussion of available annotation sources and a demonstration of how these annotations may be utilized in VarSeq filter chains to identify clinically relevant CNVs. We will also discuss CNV assessment catalogs as a mechanism for tracking common CNVs and identifying relevant previously classified events.
October 10, 2018
Golden Helix has created VSWarehouse as a solution to store the massive collection of sample and variant data output from your tertiary analysis. The classic VSWarehouse application provides a means of storing and querying on all your variant data from VarSeq projects. On top of storing your variants, VSWarehouse also stores your assessment catalogs and clinical reports. Regarding VarSeq,..
September 26, 2018
Although the latest reference genome (build 38) was released in 2009, it has taken quite a while to come into its own as a baseline for the clinical interpretation of variants in human disease. A lot of this was momentum, while some of it was concerns about compatibility with other labs and published literature. Yet the largest hindrance was the lack of support of the bioinformatic tools and requisite databases required to analyze variants. When we released VSClinical, we wanted those concerns to be removed from the choice of what reference genome a lab may choose to use...
September 12, 2018
Copy number variations (CNVs) are characterized by a deletion or duplication of segments of the genome and can alter many properties of genes and their functionality. As such, CNVs are known to contribute to a considerable number of Mendelian disorders including developmental delays, spinal muscular atrophy, autism, Alzheimer disease, and schizophrenia. With the increasing knowledge of the impact of CNVs on the human genome, it is essential to have software that can identify these structural variations...
August 15, 2018
Processing variants related to cancer is an incredibly critical process and a primary goal is to not only assess the variants rapidly but also accurately. A major improvement to cancer panel workflow efficiency is to utilize VarSeq for variant filtering, annotating, and interpretation. In this webcast we’ll cover some important quality assurance capabilities VarSeq provides, multiple approaches to build targeted panels...
July 11, 2018
We recently have exposed the powerful application of our newly released product, VSClinical and the included ACMG Guidelines. Our previous webcasts covered some basics on new algorithms and annotations behind the variant scoring and classification. Taking a step back for a moment, there are many long-time VarSeq users are familiar with our Trio template that comes packaged with the software. But, how does the Trio analysis fit into VSClinical?
June 6, 2018
Clinical Genetic testing requires a complex analysis using the totality of our knowledge about the clinical relevance of a variant and a gene. This includes bioinformatic evidence as well as clinical evidence. The ACMG Guidelines provided a framework in which to score variants based on this evidence, and while some of those scoring criteria require close consultation of the clinical context for a given patient, much of it can be automated...
May 16, 2018
Computational evidence plays a vital role in the interpretation of variants using the ACMG guidelines. This includes functional prediction scores like SIFT and PolyPhen2, as well as conservation metrics such as GERP++ and PhyloP. In this webcast, we will review the conservation scores and functional prediction algorithms available in VSClinical. This will include a discussion of our own implementation of these algorithms...
May 2, 2018
To fully interpret variants in the context of clinical genomics, as outlined by the ACMG interpretation guidelines, variants near canonical splice boundaries must be evaluated for their potential to disrupt gene splicing and thus be classified as a gene-damaging mutation. Five splicing methods have been canonized for this purpose in the clinical testing market: GeneSplicer, MaxEntScan, NNSplice, and Position Weight Matrix (PWM)...
April 18, 2018
We have seen the widespread adoption of VarSeq in the clinic. It is chosen for its versatility and flexibility as well as the extensive catalog of annotations provided by Golden Helix. In a genetic testing scenario, VarSeq provides the annotated and filtered list of high-quality variants to that are ready for the user to classify and interpret...
April 4, 2018
Copy number variations (CNVs) are associated with a variety of genetic disorders including autoimmune diseases, autism, and cancer. VS-CNV gives clinicians and researchers the ability to detect both large and small CNV events, annotate them against a wide array of useful data sources, and perform filtering to obtain a small set of clinically relevant variations. In this webcast, we will discuss methods for adjusting algorithm sensitivity, leveraging CNV assessment catalogs, and excluding problematic CNV calls....
March 14, 2018
Infectious diseases pose significant threats to the catfish industry. Enteric septicemia of catfish (ESC) caused by Edwardsiella ictaluri is the most devastating disease for catfish aquaculture, causing huge economic losses annually. Channel catfish and blue catfish exhibit great contrast in resistance against ESC, with blue catfish being highly resistant. As such, the interspecific hybrid backcross progenies provide an ideal system for the analysis of resistance QTL...
February 28, 2018
Cancer is a genomic disease where the accumulation of genetic mutations in somatic cells contributes to tumorigenesis and metastasis. Accurate characterization of somatic mutations in tumors is crucial for personalized cancer treatments in clinical care. In collaboration with Golden Helix, Sentieon Inc. provides industry-standard tools for processing next-generation sequencing data, including tools that match the somatic variant callers MuTect and MuTect2 with over 10x speedups, scalable multithreading, no downsampling and improved determinism...
February 14, 2018
Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, characterized by premature atherosclerotic cardiovascular disease. FH affects an estimated 1 in 250 individuals worldwide, and is considered to be the most frequent monogenic disorder encountered in clinical practice. Although FH has multiple genetic etiologies, the large majority of defined cases result from autosomal codominant mutations in the LDL receptor gene (LDLR).
January 10, 2018
Next-generation sequencing has enabled clinicians and researchers alike to identify novel genetic variants associated with rare Mendelian Diseases across the human genome. To help enable researchers and clinicians understand the role of CNVs in human health and disease, Golden Helix has integrated a specialized NGS-based CNV caller capable of detecting deletion and duplication events as small as single-exons and as large as whole chromosome aneuploidy events. In this webcast, we will present our workflows that integrates the NGS-based CNV caller into SVS.
December 13, 2017
Predicting phenotypic traits from genotypes is a key focus in agrigenomics, as researchers and commercial farming operations work to increase crop yields and meat production to satisfy the needs of a growing global population. Genomic prediction allows these scientists to identify the plants or animals with the best breeding potential for desirable traits without having to go through lengthy and expensive field trials.
Whole Genome Structural Analysis of Caribbean Hair Sheep reveals quantitative link to West African Ancestry
November 15, 2017
Drug resistant parasites are a rising concern to the livestock industry. Caribbean hair sheep are known to be parasite resistant and are especially recognized for robust performance in the presence of gastrointestinal nematodes. Hair sheep have become an important part of the U.S. sheep industry. Lack of wool eliminates a number of health concerns and drastically reduces the cost of production. Despite the growing importance of hair sheep in the Americas their genetic origins have remained speculative. In this presentation, we combine historical research with archeological evidence and modern day computational genomic methods to uncover the unique ancestry of these breeds.
October 11, 2017
Next-generation sequencing has enabled clinicians and researchers alike to identify novel genetic variants associated with rare Mendelian Diseases across the human genome. To help enable researchers and clinicians understand the role of CNVs in human health and disease, Golden Helix has a fully integrated CNV annotations to provide clinicians and researchers with more effective methods to identify pathogenic CNVs for heritable diseases. In this webcast, we will present our comprehensive clinical workflows that integrates the annotating and reporting of high-quality CNV alongside their existing NGS variants.
September 27, 2017
While Copy Number Variants are important to detect and interpret in many clinical genetic tests, labs have been without a comprehensive solution that integrates the annotating and reporting of high-quality CNV alongside their existing NGS variants.
Golden Helix has developed and validated with our clinical partners a specialized NGS-based CNV caller capable of detecting deletion and duplication events as small as single-exons and as large as whole chromosome aneuploidy events.
September 13, 2017
Darby Kammeraad, Field Application Scientist at Golden Helix, gives some insight into the advantages of VarSeq’s capability with annotations. The number of annotation topics to cover are seemingly limitless. In this webcast, he focuses on key elements that demonstrate the value of Golden Helix’s curated annotations available in VarSeq and address some important considerations from our users. We also cover the types and effective utilization of annotations in VarSeq. Finally, he covers how users can create their own annotation sources from the Convert Wizard tool.
August 9, 2017
In this webcast we focus on the recent improvements to our research product SNP & Variation Suite. Over the past 12 months, we have continued to expand on the tools SVS provides to the researcher doing association studies, whether from standard GWAS workflows or complex custom Large-N studies. Based on user requests, we have added features from a couple recent papers and their corresponding method packages to compute heritability estimates, understand the genetic correlation between two traits and improve our GBLUP methods to correct for gene by environmental factors.
July 12, 2017
In this webcast, we feature several example workflows and helpful features in the VarSeq that can be used in the clinic. We discuss options for conducting a comprehensive gene panel analysis for cancer or hereditary diseases. Then we introduce an example of a single exome workflow that goes from an unfiltered VCF created by a secondary analysis pipeline to a report containing information about interesting variants. Finally, we walk through an example of a trio analysis showcasing a variety of different filter options as well as inheritance patterns. All these workflows will result in a customizable clinical report.
June 7, 2017
In this webcast we will provide an overview of our complete end-to end clinical stack. Initially we will walk through our powerful secondary analysis pipeline which allows you to call SNVs and CNVs. We will demonstrate how various types of CNVs are called and discuss metrics that express the confidence associated with each call. We then show our powerful tertiary analysis capabilities for gene panels, exome and whole genome data. And finally, we demonstrate how our users can move seamlessly from the variant interpretation stage to a clinical report.
The Sentieon Genomic Tools - Improved Best Practices Pipelines for Analysis of Germline and Tumor-Normal Samples
May 17, 2017
The Sentieon Genomics Tools provide identical results to the GATK pipelines with a 10x reduction in runtime, a robust software implementation, and deterministic data processing. This webcast will explore the benefits of the Sentieon Genomics Tools including a discussion of the results of the PrecisionFDA Truth and Consistency challenges and the ICGC-TCGA DREAM Mutation Calling Challenge for somatic SNV, indel, and structural variants. Golden Helix has partnered with Sentieon to integrate its secondary analysis tools with Golden Helix software to provide users with a comprehensive solution for genomic data analysis. In this webcast, Dr. Andreas will delve into the new partnership, followed by a demonstration of the Sentieon software by Dr. Donald Freed.
May 3, 2017
Dr. Jingga Inlora is a postdoctoral fellow in the Snyder lab at Stanford University. In this webcast, Inlora will present on her team's recent study focused on identifying genetic variants associated with rare Mendelian Diseases. In this webcast, discusses four cases of Mendelian disorders observed in affected families. Using WES and bioinformatics techniques, her team identified variants in each disease case, which co-segregates with the disease and are compatible with the phenotype.
April 19, 2017
Clinical labs must have the ability to go from a collection of samples to a professional report documenting a short list of clinically relevant variants and copy number variants. Copy number variants (CNVs) in particular play an important role in human health and disease, and the detection of CNVs in clinical samples has the potential to improve clinical diagnoses and inform treatment decisions. The VarSeq CNV Algorithm (VS-CNV) has been developed to help facilitate this analysis in a single algorithm that can be run in conjunction with your variant analysis. In this webinar, we will discuss the typical CNV workflow from a VarSeq user’s perspective.
April 5, 2017
Dr. Reza Sailani is a Research Fellow in the Genetics department at Stanford University. To provide an overview of his research, Sailani presents on two recent studies he has conducted. The first is Association of AHSG with alopecia and mental retardation (APMR) syndrome, which focused on WES sequencing results of a large consanguineous family segregating APMR syndrome with seven affected family members. The second is Identifying genetic determinant of essential tremor in which the team performed whole exome sequencing for a large ET-affected family.
March 8, 2017
Next Generation Sequencing Exomes are a powerful assay used in both clinical and research settings to discover novel and rare small variants. Now a mature part of many labs, exomes consistently provide coverage over hundreds of thousands of targets across the genome. Along with the small variants, exomes can also be used to call Copy Number Variations, providing extra value for data you may already have and discovering events that may not be captured by any of your existing testing technology.
Watch as we review the next generation CNV and LOH calling algorithm coming to VarSeq and provide case-studies and examples of the capabilities of this algorithm and how it fits into the existing powerful VarSeq platform
February 15, 2017
Clinical labs need to be able to process samples down to a short list of variants and publish a professional report. VSReports helps scientists and clinicians alike create timely, actionable reports that can improve clinical decision making and streamline patient care by seamlessly incorporating the results of tertiary analysis into a customizable clinical report.
Reports are fully customizable, containing focused and actionable data. Additionally, reports can be branded and styled to match the documents that your lab typically produces. With tight integration to your analysis results, you can also pull in additional annotation sources relevant to the sample being tested.
This webcast will walk through preparing a template for report generation, reviewing the generated report and performing some report customizations.
January 11, 2017
Genotype imputation is a common component of many analytical workflows on microarray data.
At Golden Helix, we have worked hard over the years to make SNP & Variation Suite a one-stop shop for all SNP-based large N analytical workflows, and so it makes sense to add a robust and powerful genotype phasing and imputation engine. With the publication this year “Genotype Imputation with Millions of Reference Samples” in AJHG, the Brownings have demonstrated yet again the capabilities and performance of the Beagle algorithm package.
Join us in this webcast to see how we have written an open-source C++ port of Beagle v4.1 that is fully integrated into SVS and allows you to run your genotype phasing and imputation on human and animal data as part of your SVS analytics workflow.
December 7, 2016
Numerous studies have documented the role of Copy Number Variations (CNVs) in human health with associated phenotypes including cancer, obesity, cognitive disability and numerous other maladies. Yet currently, detection of CNVs on targeted gene panels requires an alternative assay such as Chromosomal Microarrays (CMAs). As a result, current CNV detection techniques are expensive, slow and are only capable of detecting large multi-exon events.
In this webcast, we will demonstrate a new VarSeq algorithm for calling CNVs from NGS coverage data.
October 12, 2016
Copy Number Variations (CNVs) play an important role in human health and disease, and the detection of CNVs in clinical samples has the potential to improve clinical diagnoses and inform treatment decisions. Yet until now, if you wanted to have CNVs on your targeted gene samples, you would need an alternative assay such as Chromosomal Microarrays (CMAs).
While we consider the handling of the variety of target panels and exome capture scenarios a process of iterative improvement, we will demonstrate the high precision characteristics of our algorithm on our clinical validation data sets.
September 21, 2016
Every day, the trove of genomic data is growing.
Clinics are sequencing targeted genes at high read depths to report out genetic tests. Research groups are adding new exomes and genomes to their disease specific cohorts. Agricultural breeders are genotyping their herds and flocks by the thousands of thousands.
The conventional attitude to big data is give up using your existing workstations and servers and fully commit to an alternative universe of computation: clusters of computers run by complex management systems, opaque distributed file systems only accessible by specialized tools and software completely rewritten for this specific and often proprietary platform. At Golden Helix, we believe there is an alternative approach.
September 7, 2016
One of the main recent advances in cancer therapy is the identification of medications that target specific gene mutations. In 2001 Gleevec was approved to treat patients with the BCR-ABL fusion in chronic myelogenous leukemia (CML), but since then many more drugs have been developed. Currently, there are numerous ongoing trials to identify tumor drivers that can be attacked by a drug. In order to identify the mutations driving a tumor, the tumor needs to be sequenced. There are a range of different approaches for sequencing tumors ranging from the sequencing of a few genes in the tumor up to paired whole-exome sequencing in both the tumor and adjacent normal tissue. Each type of sequencing has benefits and drawbacks and a balance needs to be made between cost and usability of the results. We have developed a clinical workflow for a 50 gene panel that identifies mutations in hotspots in known cancer genes. This workflow uses BaseSpace, VarSeq and N-Of-One to provide insight for our physicians and patients.
August 10, 2016
Molecular genetic research has supported the use of a multivariate phenotype representing alcohol dependence in studies of genetic association. One recent study found that additive genetic effects on Diagnostic and Statistical Manual of Mental Disorder version four (DSM-IV) alcohol dependence criteria overlap, describing a common pathway model that consists of a single latent variable representing alcohol dependence (Palmer et al. 2015). Common single nucleotide polymorphisms (SNPs) explained 31% of variance in this latent factor. However, these findings were conducted using a sample of European Americans and minimal research exists to provide insight into whether this finding is consistent in a population of African descent. Using a large sample of individuals from European and African ancestry, we investigated the extent to which additive genetic variance tagged by common SNPs explain variation in alcohol dependence and whether these markers are shared across the two populations.
July 13, 2016
VarSeq Reports can be used as part of an automatic pipeline to quickly list variants with information that can be used to make actionable clinical decisions in a readable HTML format. Need to further filter the variants or add interpretation and recommendations? No problem! Clinical reports are easy to review, edit and prepare.
This webcast will walk through preparing a template for automatic report generation, running new data through the pipeline and reviewing the generated report.
June 8, 2016
Using WES in distant relationships to identify cardiomyopathy genes Cardiomyopathy (DCM; MIM 115200) are myocardial diseases that are frequently hereditary, yet remain gene-elusive for 60% of affected families. Traditional gene discovery techniques dependent on multigenerational samples are difficult to apply. This is because 1. Disease is often impenetrant in the youngest generation, 2. Samples are often not available in the oldest generation and 3. Incomplete penetrance and variable expressivity are common across all generations. However, a detailed family history will often identify definitively affected but distantly related individuals. Such families are highly powered for gene discovery using whole exome sequencing (WES) and analysis in SNP and Variation Suite (SVS) software.
May 11, 2016
VarSeq contains default workflows for Trio analysis which include filter chains for identifying de Novo and Compound Heterozygous variants, but what if you have data for a full Quad or even just a few siblings? How could your VarSeq workflow be adjusted to handle this custom family structure?Watch the recording »
April 20, 2016
The Canadian Pharmacogenomics Network for Drug Safety (CPNDS), recently discovered a novel gene (RARG) responsible for cardiomyopathy and congestive heart failure in cancer survivors and has developed clinical practice recommendations for genetic testing to reduce the incidence of anthracycline-induced cardiotoxicity in children after cancer treatment.
Join us as Dr. Folefac Aminkeng, presents the CPNDS’ important research efforts focused on understanding the role of genes in ADRs and developing drug safety solutions for cancer patients, initiatives which are critical to improving long-term survival outcomes.
April 6, 2016
As the number of samples and associated data volume in a testing lab increases, it becomes imperative for labs to leverage state of the art warehousing technology that not only organizes data, but also aides and enables researchers and clinicians to perform further analysis, and ongoing research.
Built on the algorithms and high-performance storage technology that powers the VarSeq software, VSWarehouse offers a scalable, multi-project warehouse for NGS variant call sets, clinical reports, and a knowledge base of variant classifications.
March 2, 2016
Clinical labs must have the ability to go from a collection of samples and associated variants to a professional report documenting a short list of clinically relevant variants. Cancer Gene Panels are a common clinical application for genetic tests. In this webcast we will show how VarSeq and VSReports can be used to go from an unfiltered variant file created by a secondary analysis pipeline to a report containing information about interesting variants.
February 3, 2016
As Precision Medicine is taking off, the number of samples in a testing lab and the associated data volume is increasing exponentially. In order to organize the data and build a knowledge base of cases that can be used for future analysis as well as ongoing research, labs need to leverage state of the art warehousing technology.
January 20, 2016
Genome-wide association studies (GWAS) have been providing valuable insight to the genetics of common and complex diseases for many years. In this webcast we will walk through one possible workflow for completing GWAS in Golden Helix SNP & Variation Suite (SVS) with special attention paid to adjusting analysis for population stratification.
November 4, 2015
Clinical labs need to be able to process samples down to a short list of variants and publish a professional report. Two common clinical applications for genetic tests include Cancer Gene Panels and Whole Exome Trios. Using VarSeq and VSReports, we will demonstrate how easy it is to go from a variant file created by a secondary analysis pipeline containing unfiltered variants to a report containing information for variants of interest. Along the way we will discuss tips and tricks and answer frequently asked questions to help you get the most out of your data!
October 14, 2015
The genetic etiology of neurodevelopmental disorders has proven elusive due to the substantial phenotypic and etiological heterogeneity of their common forms. Developmental language disorders affect approximately 7% of children and are associated with negative outcomes in a multitude of domains, including social, emotional, behavioral, and academic functioning. Yet, with the exception of several reported monogenic cases, they are severely understudied with respect to their genetic bases, as the field is effectively only entering its 'GWAS era'.
One of the possible solutions is to reduce the supposed phenotypic and locus heterogeneity by studying special populations such as genetic isolates. Taking this approach, Dr. Sergey Kornilov and Dr. Elena Grigorenko's team at Yale University performed a genome-wide association and whole exome sequencing study of members of a unique geographic Russian-speaking isolate, characterized by an unusually high prevalence (i.e., around 30%) of neurodevelopmental disorders of speech and language.
September 23, 2015
As labs move genetic tests into production using VarSeq, we have been looking for ways to support more of their total workflow within the same integrated expertise used to annotate, filter and interpret variants. With our upcoming release of VarSeq, we are introducing a powerful and flexible platform to author clinical reports, specialized to the needs of individual labs and tests.
This webcast shows the new VarSeq Reports add-on feature, as well as other components of the total clinical test workflow.
September 9, 2015
Currently, ALDH7A1 is the only gene for which mutations are known to underlie PDE. However, locus heterogeneity has been reported in some families and other genes seem to be involved. Nearly 5% of children with a typical clinical picture of PDE harbor no detectable mutation of ALDH7A1. Identifying causative genes in such families will likely lead to improved treatment for these patients and help unravel much of the unknown about pyridoxine metabolism in the human body.
In this webinar, Hilal will cover how he and his team used whole-genome SNP genotyping, genome-wide runs of homozygosity (RoH) mapping using SVS, and whole-exome sequencing to characterize the genetic defect underlying PREE in a consanguineous Omani Arab family with two affected children who have a PDE-like clinical picture but negative ATQ biomarkers.
August 12, 2015
Although individuals with sickle cell anemia ostensibly have a monogenetic disease, they exhibit wide variability in the degree of clinical severity. One of the most powerful and reproducible predictors of disease severity is the level of endogenous fetal hemoglobin (HbF), composed of two gamma-globin and two α-globin chains. Expression of HbF is reduced in infancy and little is known about how this regulation is accomplished. A better understanding of gamma-globin regulation could aid in the discovery and design of a specific gamma-globin inducing agent.
Taking a genomics approach to this question, Dr. Vivien Sheehan and her team investigated the natural human variation and its correlation with HbF levels to identify novel genes important for gamma-globin regulation. In this webinar, she describes how they performed whole exome sequencing (WES) and used gene-based analysis to find correlations between rare variants and endogenous HbF levels.
July 8, 2015
Dr. Raluca Mateescu does research in the area of beef cattle, sheep and goat molecular genetics. Most biological traits of economic importance in domestic animals have a complex inheritance (are influenced by many genes and the environment) and the long-term research goal is to unravel the genetic basis for the phenotypic variability in this type of trait. Her research uses recent advances in the animal genomics field with the goal of improving animal production efficiency and enhancing animal products for improved human health.
In this webinar Dr. Mateescu will focus on use of SVS program to perform genome-wide association studies for individual traits describing beef palatability, identify chromosomal regions associated with these traits, estimate genomic breeding values and predict the accuracy of GEBV for palatability traits in beef.
June 10, 2015
Many questions must be answered when analyzing DNA sequence variants: How do I determine which variants are potentially deleterious? Is the sequencing quality sufficient? How do I prioritize the results? Which annotation sources may help answer my research question?
In this webinar presentation, we will review workflow strategies for quality control and analysis of DNA sequence variants using the VarSeq software package from Golden Helix. VarSeq is a powerful platform for analysis of DNA sequence variants in clinical and translational research settings. VarSeq provides researchers with easy access to curated public databases of variant annotation information, and also enables users to incorporate their own local databases or downloaded information about variants and genomic regions.
May 13, 2015
We are excited to announce and demonstrate some new and highly requested features in this webcast, including predicting phenotypes by applying existing GBLUP or Bayesian models and meta-analysis for GWAS studies.
Recently in SVS we added additional genomic prediction tools such as Bayesian Genomic Prediction and K-Fold Cross Validation. We have continued to build out the prediction suite of tools by adding the ability to apply the results of a model to a new genomic dataset to predict the phenotype. This is designed to work hand-in-hand with the output of K-Fold cross-validation using either GBLUP or Bayes C/C-pi.
April 15, 2015
The power of VarSeq's project-based repeatable workflows has already been adopted by clinical labs such as NorthShore University HealthSystem and Prevention Genetics, and we continue to build features to support the compliance and data privacy requirements of a clinical environment. This webcast highlights some of our new features for supporting gene panel screenings and rare variant diagnostics.
March 25, 2015
The premedical competencies as outlined in a recent American Association of Medical Colleges (AAMC)-HHMI report on Scientific Foundation for Future Physicians calls for stronger connections between course content and the underlying principles in health and medicine. To meet this need, I am developing chemistry courses at the University of Illinois for pre-health professionals that teach concepts and content in a personally meaningful way, thereby stimulating deep student interest and promoting curiosity-driven learning. Scientific evidence shows that people who feel curious devote more attention to an activity, process information more critically, remember information more effectively and persist on task until goals are met.
March 11, 2015
Cancer is a leading cause of death in developed countries. In this webcast Dr. Andreas Scherer will explain how personalized medicine can transform our approach to fighting this disease. He will also discuss current roadblocks and diagnostic challenges, and the pivotal role of Next Gen Sequencing to overcome these challenges.
February 11, 2015
It is often possible to gain additional insights into your GWAS data by looking beyond individual SNP associations to consider more complex genetic features, such as haplotypes or homozygous segments. Some haplotypes may have stronger trait associations than are observed for the constituent SNPs. Analyzing runs of homozygosity (ROH) may reveal associations with recessive haplotypes or identify loci with multiple associated alleles.
January 21, 2015
Many of today's researchers are generating DNA sequence data for large numbers of samples in population-based experiments. This may include whole genomes, exomes, or targeted regions. The Golden Helix SNP and Variation Suite (SVS) provides a powerful computing environment for analyzing these data and performing association tests at the gene and/or variant level.
December 16, 2014
Predicting phenotypic traits from genotypes is a key focus in agrigenomics, as researchers work to increase crop yields and meat production to satisfy the needs of a growing population. Genomic prediction allows these scientists to identify the plants or animals with the best breeding potential for desirable traits without having to endure lengthy and expensive field trials.
November 5, 2014
Golden Helix recently announced the forthcoming public release of VarSeq, a powerful new application for interpretation of DNA sequence variants. VarSeq is designed to make variant analysis workflows fast, simple, interactive, and repeatable.
October 1, 2014
We introduce to you: VarSeq! VarSeq is a next generation tool designed around a focused and intuitive user interface for analyzing Next Generation Sequencing data, powered with the same mature Golden Helix core technology for data management, annotation, and visualization.
September 23, 2014
RNA-Seq analysis is the newest area of functionality in the Golden Helix SNP and Variation Suite (SVS) software. SVS offers a wide range of tools for analyzing and visualizing RNA-Seq data, with a particular focus on differential expression analysis. In this presentation, we will demonstrate some of these options using a mouse dataset downloaded from Gene Expression Omnibus (GEO) as a case study, including available functions for data summaries and quality checks, data visualization including heat maps, interactive visualization in GenomeBrowse, and statistical methods for differential expression analysis, including DESeq.
August 26, 2014
This webcast will discuss the benefits of genomic prediction for trait optimization, how to set up training and validation datasets, cover the highlights of the GBLUP method, and demonstrate genomic prediction and training/validation using GBLUP in Golden Helix's SNP and Variation Suite (SVS) software. We will use two datasets for the demonstration portion of the webcast, one plant dataset and one animal dataset.
August 6, 2014
In this webcast, Ashley Hintz, Field Application Scientist, will address some common topics fielded by our support team. Topics include working with custom genomes, making collated spreadsheets, and activating/inactivating data.
July 22, 2014
The genetic improvement of livestock has been a hot topic for almost a century, bringing together researchers, industry, and producers to work towards a common goal. Many countries currently employ extensive genetic selection programs in their cattle with pigs, sheep, and chicken close behind. In this webcast, Heather J. Huson, Ph.D. from Cornell University will focus on population dynamics and trait association in cattle and goats using high density SNP datasets.
July 9, 2014
GWA studies are perhaps most often used for studying the genetic basis of human diseases, but this technology also has great utility for studying the natural variation of other organisms. In this webcast, Ashley Hintz, Field Application Scientist, will discuss the utility of SVS for analyzing plant GWA data, using publicly available SNP data for Arabidopsis thaliana as a case study. Along the way, Ashley will demonstrate how SVS can be used to manage data, analyze population structure, perform genotype QA and ultimately replicate a published genetic association in A. thaliana using EMMAX regression. She will also address the flexibility of SVS for analyzing the genomes of other plant and animal species.
June 10, 2014
Confounding from population structure, extended families and inbreeding can be a significant issue for burden and kernel association tests on rare variants from next generation DNA sequencing. An obvious solution is to combine the power of a mixed model regression analysis with the ability to assess the rare variant burden using methods such as KBAC or CMC. Recent approaches have adjusted burden and kernel tests using linear regression models; this method adjusts for the relatedness of samples and includes that directly into a logistic regression model.
Examining the Genetic Underpinnings of Commonly Comorbid Language Disorders: Dyslexia and Language Impairment
May 13, 2014
Written and verbal language are vital to the development of communication skills. Unfortunately, disorders of these traits—specifically reading disability (RD) and language impairment (LI)—are common, leaving affected individuals at risk for adverse academic, socioeconomic, and psychiatric outcomes. RD and LI are complex traits that frequently co-occur, leading to the hypothesis that these disorders share genetic contributors.
April 16, 2014
Most NGS analysis is founded on a very simple and powerful principle: look only at the differences of your data to a reference genome of your species. Alignment algorithms are the workhorse of this approach and accounts for the vast majority of the compute time necessary in a secondary analysis workflow. In this webcast, Gabe Rudy covers the history of alignment algorithms of short read, high-throughput sequencing data and the set of tools that represent the state of the art.
March 11, 2014
SNP & Variation Suite (SVS) is an integrated collection of powerful analytic tools for managing, analyzing, and visualizing multifaceted genomic and phenotypic data. Applications include next-generation sequencing studies (DNA/RNA), genome-wide association, and copy number analysis. Golden Helix introduces a major upgrade to the product used by hundreds of organizations around the world to accelerate their research.
February 19, 2014
In this webcast, Gabe Rudy, Vice President of Product Development, will showcase publicly available databases and resources available for interpreting rare and novel mutations in the context of his own personal exome obtained through a limited 23andMe pilot in 2012. The last couple years have seen many changes in well-established resources such as OMIM and dbSNP, while motivating new efforts such as ClinVar and PhenoDB to bring NGS interpretation to clinical grade through a global data sharing effort.
February 4, 2014
In this webcast, Dr. Christensen will cover: options for getting GWAS and sequence information online without any associated cost, tips for working with these datasets and what you'll see in terms of data quality and usefulness, how to use public data sources in conjunction with your GWAS or sequence study (and how NOT to), and data management and manipulation features in SNP & Variation Suite to more effectively utilize online databases.
January 8, 2014
In this webcast, Greta Linse Peterson will present updated workflows in SNP & Variation Suite 8 (SVS) and GenomeBrowse for agricultural genetic research. SVS includes a robust suite of analytical tools and a revolutionary genome browser in one program to support a wide-variety of species including plant, animal, and parasites. New tools make it easy to adjust for inbreeding and incomplete pedigrees, making it even easier than before to identify variants related to pest and disease resistance, increased feed efficiency, milk production, and more.
December 11, 2013
Genome-wide association studies (GWAS) have been providing valuable insight to the genetics of common and complex diseases for nearly 10 years. Despite some assertions to the contrary, GWAS is not dead. GWAS is alive and well, and remains a viable technology for genetic discovery. This webcast covers: GWAS data formats, usability, and data management techniques, imputation, quality assurance, genotype association testing and statistics, and visualization. Along the way, Dr. Christensen highlights best practice approaches and common pitfalls to avoid.
November 13, 2013
Analysis of rare variants for population-level data is becoming a more common component of genomic research. Whether using exome chips, whole-exome sequencing, or even whole-genome sequencing, rare variation analysis requires a unique analytic perspective. In this presentation, we will review some of the tools available in SVS for large sequenced cohorts including summarization, visualization, and statistical analysis of rare variants using KBAC, CMC, and other methods.
October 30, 2013
Researchers who are new to NGS data analysis will learn techniques commonly utilized in small-N sequencing workflows whereas experienced SVS users will discover more streamlined or "one-off" solutions to complement their advanced processes. The workflow for small-N trio data will cover three main aspects: data preparation, initial investigation, and variant analysis. To effectively showcase this workflow, Autumn will also highlight the online SVS Scripts Repository, which is home to several well-tested and high-quality tools that can become part of your analytic toolbox.
Repeating a workflow that involves several different quality control, filtering, and analysis steps is burdensome and error-prone. To solve this problem, we introduce custom workflow automation in SVS, which allows you to collapse dozens of steps into a few run-specific options. This click-and-go process saves an exponential amount of time while eliminating the inevitable user error that happens with tedious repetition and ensures that the exact same protocol is followed with each run, a critical requirement for use in the clinic.
July 24, 2013
This webcast will demonstrate the ability of GenomeBrowse to stream sequence alignment data from the Amazon Cloud, seamlessly transitioning between whole genome views and base-pair resolution in the context of both public and custom annotation tracks. We will show how GenomeBrowse can be used in conjunction with SVS to highlight false variant calls, confirm the inheritance pattern of putative functional variants, and aid in the interpretation of a variant's impact. Examples of RNA-seq expression analysis, somatic variation in cancer, and family-based DNA-seq analysis will be included.
June 5, 2013
This presentation will review four different methods of analyzing genotype data while accounting for random effects of relatedness. Methods include PCA analysis with Linear Regression, GBLUP, EMMAX, and MLMM. Comparisons will be made using data from the Sheep HapMap project and a simulated phenotype. After presenting the various methods, we will discuss how these results can be obtained using Golden Helix SNP & Variation Suite (SVS) software and how SVS can be used to compare and contrast the results.
May 15, 2013
This presentation will review several of the functional prediction tools that are currently available to help researchers determine the functional consequences of genetic alterations. The biological principals underlying functional predictions will be discussed together with an overview of the methodology used by each of the predictive algorithms. Finally, we will discuss how these predictions can be accessed and used within the Golden Helix SNP & Variation Suite (SVS) software.
March 27, 2013
This presentation will compare the performance of the alignment and variant calling tools used by sequencing service providers including Illumina Genome Network, Complete Genomics and The Broad Institute. Using public samples analyzed by each pipeline, we will look at the level of concordance and dive into investigating problematic variants and regions of the genome.
March 7, 2013
Technological advances in next generation sequencing provide clinicians and researchers with more effective methods to identify pathogenic gene mutations for heritable diseases. To date, the National Eye Institute Bank lists over 450 genes associated with eye-related disorders. Analytical processing of large datasets generated can be cumbersome for all parties involved and some issues that can cause inefficiencies include learning programming languages and reliance on inconsistent freeware. In this webcast, we demonstrate the ability to maximize Golden Helix tools to find potential pathogenic variants in rare ocular diseases.
AGBT 2013: Home Brewed Personalized Genomics - The Quest for Meaningful Analysis Results of a 23andMe Exome Pilot Trio of Myself, Wife, and Son
February 22, 2013
Personalized genomics may be moving into a new era with whole-exome and whole-genome sequencing becoming affordable and available to consumers. 23andMe recently piloted a more affordable 80x exome to their existing customers. But it remains to be seen whether this wealth of raw genomic data can be analyzed to provide meaningful results for both healthy and symptomatic individuals. By acquiring 23andMe exomes on his own family, Gabe put himself in the position of a bioinformatically inclined consumer, but non-clinician, to approach this question with his own analysis. His trio consists of a healthy father and son, and a mother with clinically-diagnosed idiopathic rheumatoid arthritis.
January 29, 2013
Since 2002, Lineagen has been building the largest proprietary collection of ASD-related genetic variants and, in 2011, spearheaded a study to increase the clinical yield of the company's genetic diagnostic test, FirstStepDx. To find candidate variants, Linegean selected the Golden Helix services team as well as the Children's Hospital of Philadelphia Center for Applied Genomics to concurrently perform quality control, analyze the data, and interpret the results. In this webcast, Dr. Hakonarson, Dr. Leppert, Dr. Paul, and Dr. Hensel outline the study and methodology approach utilized by Lineagen to achieve a two-fold increase in detection rate of genetic variants in individuals with ASD, and Dr. Christensen shares the analytic processes Golden Helix used in this valuable research.
December 5, 2012
Join Gabe Rudy as he explores his personal exome provided by the Exome Pilot project of 23andMe. Gabe will be acting as an asymptomatic consumer enthusiast as he applies the transparent techniques of high-impact variant discovery using SNP & Variation Suite (SVS) and GenomeBrowse. As he weeds out false positives and genes with low functional significance, Gabe will face the more daunting challenge of interpreting highly credible loss of function or missense variants and what if any impact that would infer to his disease risk, pharmacogenomic profile, or other annotated genomic traits.
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