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.
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
Family-Based Workflows in VarSeq and VSClinicalGolden Helix
Golden Helix is a single testing paradigm that allows users to start with next-generation sequencing data and finish with a clinical report. Our solutions are comprehensive as they are all performed in one software suite, which can save time and money as they prevent the need to outsource to different companies. Furthermore, our software is fully transparent in that you have full control over the steps performed in your analysis. Golden Helix is also on the forefront in the clinical workspace as we have implemented the ACMG and AMP guidelines to evaluate single nucleotide variants, insertions and deletions, as well as structural variants.
Beyond these functionalities, Golden Helix provides the ability to perform family-based analysis. Our ACMG and Exome trio templates give users a starting point to understand the different inheritance models ranging from transmitted to de novo variants, but we also have features that can provide additional evidence for both traditional and nontraditional family-based workflows. Specifically, we have algorithms that can be implemented to look at extended pedigree information and sample relatedness as well as options for examining whether a given variant such as a CNV segregates among similarly affected family members. In this webcast, we would like to demonstrate these features and show some solutions for the analysis of different family structures.
As an overview, this webcast will cover:
- Implementing filter logics for different family structures
- Algorithms that can be used for establishing clinical significance in family-based workflows
- Visualization capabilities for further understanding of inheritance models
- Confirming and evaluating transmitted CNVs
ClinVar: Aggregating Data to Improve Variant Interpretation - Melissa LandrumHuman Variome Project
The rate of variant discovery continues to surpass the rate of clinicalgrade interpretation. This is a challenge for precision medicine, because fast, reliable access to variant interpretations is necessary to provide well-informed and timely interpretations of test results to patients. ClinVar is a public repository for interpretations of clinical significance and functional effects of variants in any gene and for any disease. Interpretations are submitted by many sources, including clinical testing laboratories, research laboratories, locus-specific databases, expert panels, practice guidelines, as well as OMIM® and GeneReviews™. Collecting variant interpretations in ClinVar depends on integrating data from these different sources, which has several benefits. First, data integration requires standardizing the data from each source. This improves the quality of the data in ClinVar as well as in each of the individual datasets. ClinVar staff validate HGVS expressions as a routine part of ClinVar submission processing. Submitters are encouraged to use standard terms in MedGen for diseases and phenotypes. Standard terms for clinical significance are used in ClinVar when available; for example, ClinVar uses the terms recommended by ACMG to classify variants for Mendelian diseases. Secondly, ClinVar aggregates all data for a variant defined by its genomic location. Therefore, HGVS descriptions on different transcripts or on different genomic sequences can be recognized as the same variant. Thirdly, integrating data from multiple submitters allows the evidence from all sources to be pooled together. This larger collection of evidence aids the re-evaluation of variant classifications, and is especially valuable for rare variants and novel gene-disease relationships. Fourthly, data integration means that variant interpretations from different sources can be viewed together and compared. Thus a ClinVar user has access to interpretations outside any internal system and knows when there is consensus in the interpretation or not. Submitting laboratories use reports of conflicting interpretations in ClinVar to prioritize variants that they should re-evaluate. ClinVar receives data from many data providers, and therefore provides clear attribution to each contributing group, including links to records in LSDBs. Each source may update their submission to ClinVar at any time. For example, a record may be updated when a variant is re-classified or when additional evidence is available to support the interpretation. Submitters may consider providing regular updates to ClinVar to prevent their interpretations from becoming out of date. Submissions to ClinVar describe variants that range in complexity from simple alleles with explicit sequence locations through copy number changes and cytogenetic rearrangements with fuzzy boundaries.
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
Family-Based Workflows in VarSeq and VSClinicalGolden Helix
Golden Helix is a single testing paradigm that allows users to start with next-generation sequencing data and finish with a clinical report. Our solutions are comprehensive as they are all performed in one software suite, which can save time and money as they prevent the need to outsource to different companies. Furthermore, our software is fully transparent in that you have full control over the steps performed in your analysis. Golden Helix is also on the forefront in the clinical workspace as we have implemented the ACMG and AMP guidelines to evaluate single nucleotide variants, insertions and deletions, as well as structural variants.
Beyond these functionalities, Golden Helix provides the ability to perform family-based analysis. Our ACMG and Exome trio templates give users a starting point to understand the different inheritance models ranging from transmitted to de novo variants, but we also have features that can provide additional evidence for both traditional and nontraditional family-based workflows. Specifically, we have algorithms that can be implemented to look at extended pedigree information and sample relatedness as well as options for examining whether a given variant such as a CNV segregates among similarly affected family members. In this webcast, we would like to demonstrate these features and show some solutions for the analysis of different family structures.
As an overview, this webcast will cover:
- Implementing filter logics for different family structures
- Algorithms that can be used for establishing clinical significance in family-based workflows
- Visualization capabilities for further understanding of inheritance models
- Confirming and evaluating transmitted CNVs
ClinVar: Aggregating Data to Improve Variant Interpretation - Melissa LandrumHuman Variome Project
The rate of variant discovery continues to surpass the rate of clinicalgrade interpretation. This is a challenge for precision medicine, because fast, reliable access to variant interpretations is necessary to provide well-informed and timely interpretations of test results to patients. ClinVar is a public repository for interpretations of clinical significance and functional effects of variants in any gene and for any disease. Interpretations are submitted by many sources, including clinical testing laboratories, research laboratories, locus-specific databases, expert panels, practice guidelines, as well as OMIM® and GeneReviews™. Collecting variant interpretations in ClinVar depends on integrating data from these different sources, which has several benefits. First, data integration requires standardizing the data from each source. This improves the quality of the data in ClinVar as well as in each of the individual datasets. ClinVar staff validate HGVS expressions as a routine part of ClinVar submission processing. Submitters are encouraged to use standard terms in MedGen for diseases and phenotypes. Standard terms for clinical significance are used in ClinVar when available; for example, ClinVar uses the terms recommended by ACMG to classify variants for Mendelian diseases. Secondly, ClinVar aggregates all data for a variant defined by its genomic location. Therefore, HGVS descriptions on different transcripts or on different genomic sequences can be recognized as the same variant. Thirdly, integrating data from multiple submitters allows the evidence from all sources to be pooled together. This larger collection of evidence aids the re-evaluation of variant classifications, and is especially valuable for rare variants and novel gene-disease relationships. Fourthly, data integration means that variant interpretations from different sources can be viewed together and compared. Thus a ClinVar user has access to interpretations outside any internal system and knows when there is consensus in the interpretation or not. Submitting laboratories use reports of conflicting interpretations in ClinVar to prioritize variants that they should re-evaluate. ClinVar receives data from many data providers, and therefore provides clear attribution to each contributing group, including links to records in LSDBs. Each source may update their submission to ClinVar at any time. For example, a record may be updated when a variant is re-classified or when additional evidence is available to support the interpretation. Submitters may consider providing regular updates to ClinVar to prevent their interpretations from becoming out of date. Submissions to ClinVar describe variants that range in complexity from simple alleles with explicit sequence locations through copy number changes and cytogenetic rearrangements with fuzzy boundaries.
GRC Workshop held at Churchill College on Sep 21, 2014. Talk by Bronwen Aken discussing the Ensembl approach to annotating the complete human reference assembly.
Single Nucleotide Polymorphism Genotyping Using Kompetitive Allele Specific ...MANGLAM ARYA
Single Nucleotide Polymorphism
Single nucleotide polymorphism (SNP) refers to a single base change in a DNA sequence
SNP: Commonly biallelic
Two types(Based on presence in genome)
Synonymus
Non-synonymus
SNPs have largely replaced simple sequence repeats (SSRs)
Advantage of using SNPs
Low assay cost
High genomic abundance
Locus specificity
co-dominant inheritance
Simple documentation
Potential for high-throughput Analysis
Relatively low genotyping error rates
SNP genotyping platforms
BeadXpressTM,GoldenGateTM and Infinium from Illumina
GeneChipTM and GenFlexTM Tag array from Affimetrix
SNaPshotTM and TaqManTM from the Applied Biosystems
SNPWaveTM from KeyGene
iPLEX GoldTM Assay and Mass-RRAYTM from Sequonome
Variables to be considered
Throughput
Data turnaround
Time
Ease of use
Performance (sensitivity, reliability, reproducibility, and accuracy),
Flexibility (genotyping few samples with many snps or many samples with few snps),
Number of markers generated per run (uniplex versus multiplex assay capability)
Assay development requirements and genotyping cost per sample or data point.
KASP
KBioscience Competitive Allele-Specific PCR
Homogenous, Fluorescence-based genotyping technology, based on
Allele-specific oligo extension (primer)
Fluorescence resonance energy transfer
KASP Applications
Genotyping a wide range of species for various purposes.
KASP for Quality analysis, QTL mapping, MARS, and allele mining
Quality Control Analysis
QC analysis should be done for two reasons by genotyping the parents and F1s with the same subset of SNPs, in order to
confirm if F1s contains true-to-type alleles from their parents
check the genetic purity of the inbred parents.
F1s with true-to-type parental alleles for at least 90 % of the SNPs that were polymorphic between the parents should be advanced, while those with less than 10 % nonparental alleles should be discarded.
QTL Mapping
QTL mapping identifies a subset of markers that are significantly associated with one or more QTL influencing the expression of the trait of interest.
1) Select or develop a bi-parental mapping population.
2) Phenotype the population for a trait under greenhouse or field conditions.
3) Choose a molecular marking system – genotype parents of the mapping population and F1s with large numbers of markers, then select 200-400 markers exhibiting polymorphism between the parents.
4) Choose a genotyping approach, then generate molecular data for polymorphic markers
5) Identify the molecular markers associated with major QTL using statistical programs.
Large-scale allele mining
Allele mining is a promising approach to dissecting naturally occurring allelic variation at candidate genes controlling key agronomic traits.
KASP platform at CIMMYT has been used for the systematic mining of large germplasm collections for specific functional polymorphisms.
SNPs or small indels that
Presentation carried out by Sergi Beltran Agulló, from the CNAG, at the course: Identification and analysis of sequence variants in sequencing projects: fundamentals and tools .
Course: Bioinformatics for Biomedical Research (2014).
Session: 2.3- Introduction to NGS Variant Calling Analysis.
Statistics and Bioinformatisc Unit (UEB) & High Technology Unit (UAT) from Vall d'Hebron Research Institute (www.vhir.org), Barcelona.
Geared towards bioinformatics students and taking a somewhat humoristic point of view, this presentation explains what bioinformaticians are and what they do.
Flash introduction to Qiime2 -- 16S Amplicon analysisAndrea Telatin
Review of basic concepts in the 16S Amplicon analysis workflow for microbial community characterization, and brief introdution to Qiime and Qiime 2 concepts.
BiteSized seminar at Quadram Institute, UK
Event: Plant and Animal Genomes Conference 2012.
Speaker: Bert Overduin
The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) provides a comprehensive record of the world's nucleotide sequencing information, covering raw sequencing data, sequence assembly information and functional annotation. Major components of ENA include the Sequence Read Archive (SRA) for next generation data and EMBL-Bank for assembled and annotated sequences. ENA works closely together with NCBI and DDBJ as partners in the International Nucleotide Sequence Database Collaboration (INSDC). Data arrive at ENA from a variety of sources. These include submissions of raw data, assembled sequences and annotation from small-scale sequencing efforts, data provision from the major European sequencing centres and routine and comprehensive exchange with our INSDC partners. Provision of nucleotide sequence data to ENA or its INSDC partners has become a central and mandatory step in the dissemination of research findings to the scientific community. ENA works with publishers of scientific literature and funding bodies to ensure compliance with these principles and provides a portfolio of interactive and programmatic submission services to ensure the smoothest flow possible of data into the public domain. ENA data can be searched using rapid sequence similarity and text search services provided both within web-based tools and under programmatic interfaces. Data can be retrieved in a variety of appropriate widely adopted formats through a web browser and extensive REST services. This presentation will consist of an introduction to ENA, followed by a short demonstration of the various ways data can be browsed and retrieved.
GRC Workshop held at Churchill College on Sep 21, 2014. Talk by Bronwen Aken discussing the Ensembl approach to annotating the complete human reference assembly.
Single Nucleotide Polymorphism Genotyping Using Kompetitive Allele Specific ...MANGLAM ARYA
Single Nucleotide Polymorphism
Single nucleotide polymorphism (SNP) refers to a single base change in a DNA sequence
SNP: Commonly biallelic
Two types(Based on presence in genome)
Synonymus
Non-synonymus
SNPs have largely replaced simple sequence repeats (SSRs)
Advantage of using SNPs
Low assay cost
High genomic abundance
Locus specificity
co-dominant inheritance
Simple documentation
Potential for high-throughput Analysis
Relatively low genotyping error rates
SNP genotyping platforms
BeadXpressTM,GoldenGateTM and Infinium from Illumina
GeneChipTM and GenFlexTM Tag array from Affimetrix
SNaPshotTM and TaqManTM from the Applied Biosystems
SNPWaveTM from KeyGene
iPLEX GoldTM Assay and Mass-RRAYTM from Sequonome
Variables to be considered
Throughput
Data turnaround
Time
Ease of use
Performance (sensitivity, reliability, reproducibility, and accuracy),
Flexibility (genotyping few samples with many snps or many samples with few snps),
Number of markers generated per run (uniplex versus multiplex assay capability)
Assay development requirements and genotyping cost per sample or data point.
KASP
KBioscience Competitive Allele-Specific PCR
Homogenous, Fluorescence-based genotyping technology, based on
Allele-specific oligo extension (primer)
Fluorescence resonance energy transfer
KASP Applications
Genotyping a wide range of species for various purposes.
KASP for Quality analysis, QTL mapping, MARS, and allele mining
Quality Control Analysis
QC analysis should be done for two reasons by genotyping the parents and F1s with the same subset of SNPs, in order to
confirm if F1s contains true-to-type alleles from their parents
check the genetic purity of the inbred parents.
F1s with true-to-type parental alleles for at least 90 % of the SNPs that were polymorphic between the parents should be advanced, while those with less than 10 % nonparental alleles should be discarded.
QTL Mapping
QTL mapping identifies a subset of markers that are significantly associated with one or more QTL influencing the expression of the trait of interest.
1) Select or develop a bi-parental mapping population.
2) Phenotype the population for a trait under greenhouse or field conditions.
3) Choose a molecular marking system – genotype parents of the mapping population and F1s with large numbers of markers, then select 200-400 markers exhibiting polymorphism between the parents.
4) Choose a genotyping approach, then generate molecular data for polymorphic markers
5) Identify the molecular markers associated with major QTL using statistical programs.
Large-scale allele mining
Allele mining is a promising approach to dissecting naturally occurring allelic variation at candidate genes controlling key agronomic traits.
KASP platform at CIMMYT has been used for the systematic mining of large germplasm collections for specific functional polymorphisms.
SNPs or small indels that
Presentation carried out by Sergi Beltran Agulló, from the CNAG, at the course: Identification and analysis of sequence variants in sequencing projects: fundamentals and tools .
Course: Bioinformatics for Biomedical Research (2014).
Session: 2.3- Introduction to NGS Variant Calling Analysis.
Statistics and Bioinformatisc Unit (UEB) & High Technology Unit (UAT) from Vall d'Hebron Research Institute (www.vhir.org), Barcelona.
Geared towards bioinformatics students and taking a somewhat humoristic point of view, this presentation explains what bioinformaticians are and what they do.
Flash introduction to Qiime2 -- 16S Amplicon analysisAndrea Telatin
Review of basic concepts in the 16S Amplicon analysis workflow for microbial community characterization, and brief introdution to Qiime and Qiime 2 concepts.
BiteSized seminar at Quadram Institute, UK
Event: Plant and Animal Genomes Conference 2012.
Speaker: Bert Overduin
The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) provides a comprehensive record of the world's nucleotide sequencing information, covering raw sequencing data, sequence assembly information and functional annotation. Major components of ENA include the Sequence Read Archive (SRA) for next generation data and EMBL-Bank for assembled and annotated sequences. ENA works closely together with NCBI and DDBJ as partners in the International Nucleotide Sequence Database Collaboration (INSDC). Data arrive at ENA from a variety of sources. These include submissions of raw data, assembled sequences and annotation from small-scale sequencing efforts, data provision from the major European sequencing centres and routine and comprehensive exchange with our INSDC partners. Provision of nucleotide sequence data to ENA or its INSDC partners has become a central and mandatory step in the dissemination of research findings to the scientific community. ENA works with publishers of scientific literature and funding bodies to ensure compliance with these principles and provides a portfolio of interactive and programmatic submission services to ensure the smoothest flow possible of data into the public domain. ENA data can be searched using rapid sequence similarity and text search services provided both within web-based tools and under programmatic interfaces. Data can be retrieved in a variety of appropriate widely adopted formats through a web browser and extensive REST services. This presentation will consist of an introduction to ENA, followed by a short demonstration of the various ways data can be browsed and retrieved.
Advancing Agrigenomic Discoveries with Sequencing and GWAS ResearchGolden Helix Inc
Agrigenomic research is difficult enough without having to coerce software designed for human genetics to work with the plant or animal species you're studying. Not anymore.
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. Topics to be covered include: supported file formats for importing data (including imputation sources like FindHap, Fimpute, and Impute2), comprehensive sequencing and GWAS workflows to take your analysis from QA to finding putative variants or SNPs of interest, common pitfalls to avoid and precautions when working with agrigenomic data, and visualizing results seamlessly in an integrated genome browser.
Οι μαθήτριες της Α΄1 τάξης, Αχτσή Κωνσταντίνα και Βακιρτζή Ηλιάνα, δραματοποιούν τη συνομιλία του Τηλέμαχου με την Αθηνά- Μέντη, από την α΄ραψωδία της Οδύσσειας.
Leadership for Affordable Housing Evaluation Studymjbinstitute
The Leadership Program for Affordable Housing is a multi-sectoral program that was created in the context of the sharp increase in housing costs incurred by Israeli households and the belief that a concerted multi-sectoral effort is required to address the challenge.
The program was a collaboration between the Ministry of Construction and Housing and the JDC Institute for Leadership and Governance, together with senior level professional representatives from ten ministries and government agencies, local government, civil society organizations and the business sector.
It was implemented under the professional guidance of Dr. Chaim Fialkoff and Dr. Emily Silverman.
The Myers-JDC-Brookdale Institute was commissioned to evaluate the program. For more information on this or other MJB research studies, please contact us at brook@jdc.org, visit our webpage at http://brookdale.jdc.org.il/ or catch us on Facebook at https://www.facebook.com/MJBInstitute
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.
Rare Variant Analysis Workflows: Analyzing NGS Data in Large CohortsGolden Helix Inc
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.
Special attention will be given to useful functions available for download from the SVS scripts repository.
Big Data at Golden Helix: Scaling to Meet the Demand of Clinical and Research...Golden Helix Inc
With a focus on scalable architecture and optimized native code that fully utilizes the CPU and RAM available, we can scale genomic analysis into sizes conventionally considered Big Data on a single host. In this webcast, we demonstrate recent innovations and features in Golden Helix solutions that enable the analysis of big data on your own terms.
Exploring DNA/RNA-Seq Analysis Results with Golden Helix GenomeBrowse and SVSGolden Helix Inc
GenomeBrowse, a free visualization tool for all types of sequence data, was introduced in 2012 to broad acclaim. Researchers using GenomeBrowse discovered a product far beyond the status quo with seamless navigation of sequence alignments and other genomic data using a fluid, fast, and intuitive interface that just "made sense." Recent updates to GenomeBrowse, including support for VCF files and BED files and the ability to export tables of data extracted from viewable annotation tracks, further improved the product and created new synergy with Golden Helix SNP & Variation Suite (SVS).
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.
Knowing Your NGS Upstream: Alignment and VariantsGolden Helix Inc
Alignment algorithms are not just about placing reads in best-matching locations to a reference genome. They are now being expected to handle small insertions, deletions, gapped alignment of reads across intron boundaries and even span breakpoints of structural variations, fusions and copy number changes. At the same time, variant-calling algorithms can only reach their full potential by being intimately matched to the aligner's output or by doing local assemblies themselves. Knowing when these tools can be expected to perform well and when they will produce technical artifacts or be incapable of detecting features is critical when interpreting any analysis based on their output.
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.
Golden Helix's End-to-End Solution for Clinical LabsGolden Helix
In this webcast, we provide an overview of our complete end-to-end clinical stack. Initially, we walk through our powerful secondary analysis pipeline which allows you to call SNVs and CNVs. We then demonstrate how various types of CNVs are called and discuss metrics that express the confidence associated with each call.
From there, we show you our powerful tertiary analysis capabilities for gene panels, exome, and whole genome data. We show how our users can move seamlessly from the variant interpretation stage to a clinical report. Lastly, we demonstrate how our genetic data warehouse, VSWarehouse, can be used in the clinic. We also demonstrate various use cases and show how a comprehensive assessment catalog can be utilized to ensure consistent analysis across multiple labs.
We hope you enjoy our first presentation on Golden Helix's entire end-to-end solution for clinical labs!
2015 TriCon - Clinical Grade Annotations - Public Data Resources for Interpre...Gabe Rudy
The availability and details of using public genomic annotation sources to do clinical grade genomic diagnosis, using the exomes of myself, wife and son as the case study.
Darby Kammeraad, a Field Application Scientist at Golden Helix, gives some insight into the advantages of VarSeq's capability with annotations. The number of annotation topics to cover is seemingly limitless. In this webcast, he focuses on key elements that demonstrate the value of Golden Helix's curated annotations available in VarSeq and address some important considerations from our users. We also cover the types and effective utilization of annotations in VarSeq. Finally, he covers how users can create their own annotation sources from the Convert Wizard tool.
Two Clinical Workflows - From Unfiltered Variants to a Clinical ReportGolden Helix Inc
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!
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.
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.
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.
Introducing VSWarehouse - A Scalable Genetic Data Warehouse for VarSeqGolden Helix Inc
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.
MM-KBAC – Using Mixed Models to Adjust for Population Structure in a Rare-var...Golden Helix Inc
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.
Getting Started with VSWarehouse - The User ExperienceGolden Helix Inc
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.
In this presentation we will demonstrate how to customize your VarSeq workflow to handle the following family scenarios:
*Full Quad (mother, father and 2 affected children)
*Siblings with different affection status (mother, father, 1 affected and 1 unaffected child)
*No parents (2 affected siblings)
Using Clinical Reports as a part of a Gene Panel PipelineGolden Helix Inc
This webcast will walk through preparing a template for automatic report generation, running new data through the pipeline and reviewing the generated report.
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.
Population Structure & Genetic Improvement in LivestockGolden Helix Inc
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. Population structure plays a critical role in understanding the relatedness among livestock, ancestral origins of traits, and identification of unique sub-populations or breeds for production improvement and conservation. This also lays the foundation for understanding and improving species such as the goat which is a vital food source in developing countries but has little recorded production or health data.
Understanding population structure is essential for designing complex trait association studies such as those related to production and health characteristics. Here, Huson shows examples of her lab's investigation into population structure in both goats and cattle to identify distinct groups and study traits such as thermo-tolerance.
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.
MM - KBAC: Using mixed models to adjust for population structure in a rare-va...Golden Helix Inc
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.
This webcast will focus on the details of bringing Mixed Model Regression and KBAC together, including: deriving an optimal logistic mixed model algorithm for calculating the reduced model score, how the kinship or random effects matrix should be specified, and how it all comes together into one algorithm. Results from applying the method to variants from the 1000 Genomes project will also be presented and compared to famSKAT.
New Study Identifies High-Risk Variants Associated with Autism Spectrum Disor...Golden Helix Inc
A growing body of evidence suggests a genetic contribution in the development of autism spectrum disorders (ASD). 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. The results of this study were recently published in PLoS ONE: "Identification of Rare Recurrent Copy Number Variants in High-Risk Autism Families and their Prevalence in a Large ASD Population."
In this 90-minute webcast, Dr. Hakonarson, Dr. Leppert, Dr. Paul, and Dr. Hensel will 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 will share the analytic processes Golden Helix used in this valuable research.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
2. Use the Questions pane in
your GoToWebinar window
Questions during
the presentation
3. Agenda
What makes a damaging variant?
VarSeq Interactive Demonstration
2
3
4
QC Considerations
Variant analysis workflows1
4. What is VarSeq?
VarSeq
Simple
Flexible
Scalable
Variant annotation, filtering
and ranking
Repeatable workflows
Rich visualizations with
GenomeBrowse
integration
Powerful GUI and
command-line interfaces
5. Workflow Development Process in VarSeq
1. Begin from one or many VCF files
2. Annotate variants using public data sources curated by Golden Helix and/or
annotate with custom data sources.
3. Run additional computation algorithms
- Allele counts, genotype zygosity, gene list matching, etc
4. Construct filter chain to identify candidate variants
- May use combinations of logical operators in filters
- May have multiple independent filter chains and/or endpoints
5. Process results
- Gene Ranking with PhoRank
- Review variant QC
- Vizualization with GenomeBrowse
- Commit variants to local database
- Etc.
6. Annotations are the key
Good variant analysis
begins with accurate
annotations.
Golden Helix invests
extensive time and effort
in validating and
maintaining data sources.
Annotation data sources
may be used for either
quality control or analytic
purposes.
7. Defining Deleteriousness
What makes a variant potentially damaging?
Start by defining the search space:
- Rare, non-synonymous, homozygous variants?
- DeNovo mutations in highly conserved genes?
- Splice-site mutations?
- Etc.
Review annotations for remaining variants to
identify causal candidates
Which annotations to use?
8. Variant Classification
VarSeq classifies variants into
20+ different categories
The categories are further
grouped as:
- Loss of Function
- Missense
- Other
Choice of gene transcript
reference
- RefSeq
- Ensembl
- Others
9. ClinVar
ClinVar is a public archive of
variants evaluated for potential
causal relationships to diseases
Submissions from many
sources, including major clinical
laboratories
Over 100k records
Updated monthly
10. Functional Predictions
Functional predictions use algorithms to determine the expected
consequence of variants (or the resulting amino acid substitutions).
dbNSFP
- The Database for NonSynonymous Functional Predictions (dbNSFP) is a
free tool developed by Dr. Xiaoming Liu.
- Catalogs pre-computed conservation and functional prediction scores for all possible
missense SNVs in the genome
- Methods include SIFT, PolyPhen-2, MutationTaster, MutationAssessor, FATHMM, more
dbscSNV
- Companion to dbNSFP that scores variants in splice consensus regions
- Variants in these regions may disrupt normal gene expression and/or function
dbNSFP and dbscSNV are both accessible in VarSeq
11. Variant/Gene Ranking
PhoRank algorithm in VarSeq uses HPO and GO terminology to
score relationships between genes and phenotypes
Very useful to prioritize a long list of variants for individual review
Based on PHEVOR method.
13. Mappability Annotations
The human reference genome has
assembly gaps and other “difficult”
regions
NGS technology sequences short
DNA fragments which are the aligned
to the reference genome
- Most sequences are aligned correctly
- Some sequences can’t be aligned uniquely
- Some sequences may be incorrectly aligned
Luckily, we can predict many of the
trouble spots
14. Segmental Duplications
Segmental duplications are a common confounder
UCSC “Genomic Super Dups” annotation available through VarSeq
Recent Example (below):
- Apparent UPD feature in family trio was determined to be an artifact of seg. duplication
- Large chromosome segment duplicated elsewhere with >98% similarity
15. Emerging Standards
Several organizations working on best
practices guidelines for genome
mappability
- 1000 Genomes Project
- Genome in a Bottle Consortium
- Global Alliance for Genomics and Health (GA4GH)
- National Institute of Standards and Technology
Downloadable annotations available for
many types of features:
- Mappability by read length
- High G-C content regions
- Low complexity
- Segmental duplications
- Etc.
18. VarSeq Demonstration Data
Exome sequencing of five individuals from family with familial cardiac
conduction disease (CCD)
Raw sequence data obtained from SRA
19. Workflow Discussion Points
Male-to-male
transmission makes X-
linked model unlikely
May follow dominant or
recessive transmission
Inherited forms of CCD
are rare
Family has East Asian
ancestry