From gene panels to whole genome, from short to long-read sequencing, the VarSeq suite is the solution for NGS analysis and reporting in a modern clinical lab. VarSeq handles the spectrum of variant types (SNV, Indel, CNV, Fusions) and provides automated classification and reporting capabilities following the ACMG and AMP guidelines. With our new PacBio partnership, we are more adaptable than ever with creating a spectrum of custom workflows to suit our unique user needs. This webcast will review: -Data analysis scaling from Gene Panel to Genome analysis with VarSeq and VSWarehouse. -Analysis and annotation of SNVs, Indels, CNVs, and fusions. -A close look at a PacBio long-read trio analysis. Come join us for this showcase in modern VarSeq analysis capabilities.

1. From Panels to Genomes 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 to Genomes with VarSeq: The
complete tertiary platform for short and
long-read NGS data
January 17th, 2024
Presented by: Jennifer Dankoff, PhD

4. NIH Grant Funding Acknowledgments
4
• Research reported in this publication was supported by the National Institute Of General Medical Sciences of
the National Institutes of Health under:
o Award Number R43GM128485-01
o Award Number R43GM128485-02
o Award Number 2R44 GM125432-01
o Award Number 2R44 GM125432-02
o 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?
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Golden Helix is a global bioinformatics company founded in 1998
Filtering and Annotation
ACMG & AMP Guidelines
Clinical Reports
CNV Analysis
CNV Analysis
GWAS | Genomic Prediction
Large-N Population Studies
RNA-Seq
Large-N CNV-Analysis
Variant Warehouse
Centralized Annotations
Hosted Reports
Sharing and Integration
Pipeline: Run Workflows

6. Cited in 1,000s of Peer-Reviewed Publications
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7. Over 400 Customers Globally
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8. The Golden Helix Difference
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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
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FAS
Dr. Jennifer Dankoff
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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PacBio HiFi Sequencing

14. Long Read Sequencing The Holistic NGS Test
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• 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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VSClinical – AMP and ACMG Guidelines: One Suite
• Increased lab throughput
• Consistent results
• Shorten learning curve
• Staying abreast of new developments
Germline
Somatic

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VarSeq – Clinical Reports
• 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
Capabilities of the VarSeq
Suite
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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

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• Somatic Gene Panel
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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Product Demo

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22. NIH Grant Funding Acknowledgments
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
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The competitionwill run 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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