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From Panels to Genomes with VarSeq: The Complete Tertiary Platform for Short and Long-Read NGS Data
The document details a presentation by Dr. Jennifer Dankoff on utilizing VarSeq, a bioinformatics platform by Golden Helix, for short and long-read next-generation sequencing (NGS) data, particularly in cancer genetics. It highlights the integration of various workflows such as cancer panels, whole exome sequencing, and whole genome sequencing, emphasizing features like variant calling, customizable reporting, and compliance with ACMG and AMP guidelines. The presentation also covers the benefits of long-read sequencing technologies and their role in enhancing genomic profiling and analysis capabilities.
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From Panels to Genomes with VarSeq: The Complete Tertiary Platform for Short and Long-Read NGS Data
- 1. From Panels toGenomes with VarSeq: The complete tertiary platform for short and long-read NGS data January 17th, 2024 Presented by: Jennifer Dankoff, PhD
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- 3. From Panels toGenomes with VarSeq: The complete tertiary platform for short and long-read NGS data January 17th, 2024 Presented by: Jennifer Dankoff, PhD
- 4. NIH Grant FundingAcknowledgments 4 • Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under: o Award Number R43GM128485-01 o Award Number R43GM128485-02 o Award Number 2R44 GM125432-01 o Award Number 2R44 GM125432-02 o Award Number 1R43HG013456-01 o Montana SMIR/STTRMatching Funds ProgramGrant Agreement Number 19-51-RCSBIR-005 • PI is Dr. Andreas Scherer, CEO of Golden Helix. • The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- 5. Who Are We? 5 GoldenHelix is a global bioinformatics company founded in 1998 Filtering and Annotation ACMG & AMP Guidelines Clinical Reports CNV Analysis CNV Analysis GWAS | Genomic Prediction Large-N Population Studies RNA-Seq Large-N CNV-Analysis Variant Warehouse Centralized Annotations Hosted Reports Sharing and Integration Pipeline: Run Workflows
- 6. Cited in 1,000sof Peer-Reviewed Publications 6
- 7. Over 400 CustomersGlobally 7
- 8. The Golden HelixDifference 8 FLEXIBLE DEPLOYMENT On premise or in a private cloud BUSINESS MODEL Annual fee for software, training and support CLIENT CENTRIC Unlimited support from the very beginning SINGLE SOLUTION Comprehensive cancer and germline diagnostics SCALABILITY Gene panels to whole exomes or genomes THROUGHPUT Automated pipeline capabilities QUALITY Clinical reports correct the first time
- 9. Today’s Presenter 9 FAS Dr. JenniferDankoff Field ApplicationScientist
- 10. VarSeq Use Case:Cancer Panels Integrating the TSO500 workflow into VarSeq and VSClinical. • Compatible with hereditary cancer panels to somatic panel analysis. • Full spectrum of variant support. o SNPs, Indels, CNVs, and Fusions • TSO500 Cancer Panel- Integrate Genomic Signatures. o Comprehensive genomic profiling: TMB, MSI, and more. • Biomarker and gene level interpretations rendered from CancerKB. • Integration of the AMP Guidelines for Evidence Tier related drug recommendations. o Clinical Trial matching. • Fully customizable clinical reporting. Somatic Mutations Cancer Treatment Diagnosis Prognosis Indels CNVs Fusions Genomic Signatures DNA Repair Deficiency DNA Editing Mutagenesis Patterns Elevated Protein Expression SNPs
- 11. VarSeq Use Case:Whole Exome Sequencing Workflows Flexible and scalable custom workflows. • Example use cases: o Whole Exome Singleton Analysis o Trios o Carrier Status o WES Tumor/Normal Analysis • Optimize workflows for different NGS tests: o Search for variants in virtual panel. o Phenotypic matching or prioritization with PhoRank. o Include Secondary Findings. • CNV calling ranging from single exon to large aneuploidy event. o Applies to all workflow scenarios (panel, WES, WGS).
- 12. VarSeq Use Case:Whole Genome Sequencing Workflows Bringing multiple NGS tests to a single sequencing run. • Whole Genome Sequencing. o Supportfor both short and long-read sequencing. o Workflows are similar for both sequencing types. o High accuracy variant calling. o HumanPan Genome Small Variant and Structural Databases now available as VarSeq annotations. • Bringing multiple tests into one sequencing run. o Singleton sequencing instead of Trio. o Importing long-read based CNVs and SV analysis. o Up and coming: PGx • Adding VSWarehouse to the workflow for a complete solution. o Keep catalogs of variant frequencies to apply to VarSeq projects. o Store variant level interpretations. o Query saved data. o Search for changing variant classifications.
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- 14. Long Read SequencingThe Holistic NGS Test 14 • Clinically relevant propertiesof long-read sequencing o Better precision and accuracy with lower coverage across the whole genome. This is in particular helpful, identifying very rare variants with high confidence. o Improved calling of Structural Variants and CNVs. o Higher yield capturing regulatory sequences (UTRs), pseudogenes(SMN1,SMN2), centromeres, Alu elements (SINE),short tandem repeats, LINE1elements, and long repeats. o Other improvements include o Ability to providemethylation calls o Genotype phasing allows compound het analysis to be completed on a single proband. PacBio read length histogram https://www.pacb.com/technology/hifi-sequencing /how-it-works/ 2023 “Methodof the Year” – Nature Methods journal
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- 16. 16 VSClinical – AMPand ACMG Guidelines: One Suite • Increased lab throughput • Consistent results • Shorten learning curve • Staying abreast of new developments Germline Somatic
- 17. 17 VarSeq – ClinicalReports • One click option • Auto-populated data • Public and Premium databases in VarSeq • Variant interpretations in assessment catalogs • Value • Consistent report standards (according to ACMG) • Faster reporting • Customization • Multiple templates • Includes ACMG and AMP guideline-based report • Simple configurable options with in depth customization options. • Reporting formats • Excel • Word • PDF • json
- 18. Current and Future Capabilitiesof the VarSeq Suite 18 Bringing the full long-read package into the GHI workflow Sentieon, DeepVariant, others •Variants, CNVs, Breakends •BAM, CRAM •Sample manifest Secondary Analysis and External Files VSClinical •Variant interpretation •Clinical reports (Word, PDF, custom) •ACMG, AMP guidelines Interpretation and reporting VSWarehouse •Variant frequency tracking •Artifact tracking •Variant assessment catalogs VSPipeline: Command Line Automation VSWarehouse •Variant auditing •Filtering on previous results •Variant reclassification VarSeq •Filtering and annotation •Visualizing phasing •Phenotype matching •Virtual gene panels •Variant prioritization •CNV calling Tertiary Analysis Variant Storage •Tandem Repeat Analysis •Methylation & PGx PacBio •Long read sequencing: •Small variants with phasing •Structural Variants •And more! Long Read Sequencing •Tandem Repeats •Methylation & PGx
- 19. 19 • Somatic GenePanel o Cancer Classification o TSO500 Genomic Signatures o Example variant: BRAF p.Val600Glu • Whole Exome Analysis Singleton o ACMG Auto-Classification o Phenotype application with PhoRank o Report rendering o Example variant: MEF2A p.Gln427Pro • PacBio HiFi Long-Read Trio o Inheritance workflow o Secondary findings o Warehouse integration o Example variant: DNMT3A p.Cys911Tyr Today’s Workflows
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- 22. NIH Grant FundingAcknowledgments 22 • Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under: o Award Number R43GM128485-01 o Award Number R43GM128485-02 o Award Number 2R44 GM125432-01 o Award Number 2R44 GM125432-02 o Award Number 1R43HG013456-01 o Montana SMIR/STTRMatching Funds ProgramGrant Agreement Number 19-51-RCSBIR-005 • PI is Dr. Andreas Scherer, CEO of Golden Helix. • The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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- 24. Innovation Awards 24 The competitionwillrun from Dec. 1st, 2023 - Feb. 29th, 2024 So if you answer YES to one or more of the questions below, or have great examples of your workflows, then the 2024 Golden Helix Innovation Awards are for you! • Do you use Golden Helix software? • Do you use NGS analysis to treat patients? • Are you studying a particular disease category, or are you zeroing in on a specific population? • Have you incorporated the ACMG or AMP guidelines into your clinical workflow? • Do you leverage our research platform for plants, animals, or humans? • Do you work with CNVs?
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