VarSeq 2.3.0 facilitates the evaluation of a multitude of somatic genomic variations with a more refined user interface to streamline variant evaluation. Our recent webcasts have shown the full range of these newly developed upgrades: VarSeq 2.3.0: Supporting the Full Spectrum of Genomic Variation VarSeq 2.3.0: New TSO-500 and Genomic Signature Support in VSClinical AMP Now, we are showing it all in action from the user’s perspective. This webcast will provide a comprehensive demonstration of performing somatic variation analysis and reporting. We will review how to use workflow automation to expedite the NGS project creation process and report rendering. We will also demonstrate the streamlined capture of knowledge during variant evaluation by leveraging our clinical expert-curated interpretations with the Golden Helix Cancer Knowledge Base (CancerKB). We hope you will join us to see VarSeq 2.3.0 from a user’s perspective, covering: -Somatic variant workflows: necessary algorithms and filtering strategies -Import of all relevant biomarker and genomic signatures data from TSO-500 -Review content and value of clinically curated interpretations and treatments with CancerKB -Interpretation of structural variants in the VSClinical AMP Guidelines workflow -Workflow automation with VSPipeline

1. A User’s Perspective: Somatic Variant
Analysis in VarSeq 2.3.0
December 7, 2022
Presented by the Golden Helix Field Application Scientist Team
Jennifer Dankoff, PhD, Rana Smalling, PhD, and Solomon Reinman,TechnicalFAS

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3. A User’s Perspective: Somatic Variant
Analysis in VarSeq 2.3.0
December 7, 2022
Presented by the Golden Helix Field Application Scientist Team
Jennifer Dankoff, PhD, Rana Smalling, PhD, and Solomon Reinman,TechnicalFAS

4. NIH Grant Funding Acknowledgments
4
• Research reported in this publication was supported by the National Institute Of General Medical Sciences of
the National Institutes of Health under:
o Award Number R43GM128485-01
o Award Number R43GM128485-02
o Award Number 2R44 GM125432-01
o Award Number 2R44 GM125432-02
o Montana SMIR/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
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
6

7. Over 400 Customers Globally
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8. The Golden Helix Difference
8
FLEXIBLE DEPLOYMENT
On premise or in a private
cloud
BUSINESS MODEL
Annual fee for software,
training and support
CLIENT CENTRIC
Unlimited support from the
very beginning
SINGLE SOLUTION
Comprehensive cancer and
germline diagnostics
SCALABILITY
Gene panels to whole
exomes or genomes
THROUGHPUT
Automated pipeline
capabilities
QUALITY
Clinical reports correct the
first time

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10. Today’s Agenda
A User’s Perspective: Somatic Variant Analysis in VarSeq 2.3.0
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Solomon Reinman
Technical Field Application Scientist
• Somatic workflow design
• The joys of automation
Rana Smalling, PhD
Field Application Scientist
• Optimizing somatic variant evaluation
• Updates to CancerKB
Jennifer Dankoff, PhD
Field Application Scientist
• Completing an evaluation
• New report templates

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12. Basic considerations for somatic workflows
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August 2022 Webcast by Solomon Reinman - User perspective for somatic analysis in VSClinical AMP
• Common Filtering Strategies:
o Variant Quality
o Remove Common
o Gene Impact
o ACMG Classifier to remove benign variants
o Somatic/tumor panels/phenotypes
• Project versus template
• Built into template
o NGS coverage reporting
o CNV calling and analysis
o Sample demographics

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VCF &
BAM/
CRAM
Import
Annotation
& Filtering
Evaluation
& Report
• Import all major genomic variant classes,
i.e. comprehensive genomic profiling (CGP):
o SNVs/Indels
o Copy number variations
o Breakends/Fusions
o Splice variants
• Genomic signatures that describe overall state of somatic genome
• Improved automation in VarSeq 2.3.0’s VSPipeline
o Value: Increasing automation capability to 100%
VSPipeline: automating import
to clinical report

14. The Value of NGS Automation
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Test Size and Volume
• Increased number of NGS
samples
• Scale increasing from panels to
WES and WGS
• Comprehensive NGS
workflows
• Fixed cost licensing
Automation
• VSPipeline automates NGS
analysis
• CancerKB auto-applies to
evaluation biomarkers
• Scriptable AMP evaluation
• Auto-generate Clinical Reports
Warehouse
• Cohort variant frequencies
• Host Interpretation
Knowledgebase
• Integration with external
systems

15. Golden Helix CancerKB V2.0
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• High-quality expert-curated biomarker and drug
interpretations
• Accurate information, up-to-date with what is
available in the cancer field
• Each interpretation reviewed by expert curator
• Knowledge base updated monthly
• Key to VSPipeline -> VSClinical automation
• New and exciting features!

16. TSO-500 genes
Interpretation for all 523 genes
included in TSO-500 kit
Updates to CancerKB
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Copy Number
Base Substitutions
Expanded Interpretations
Increased Tier 1 and 2 interpretations
Genomic Signatures
17 new Genomic Signatures
Drug descriptions
147 new drug descriptions with indications
Combination biomarkers
Report on combinations of biomarkers
including negative findingsand
biomarker impacts
Tumor Specific FDA therapies
82 new interpretations for FDA approved
therapies at tumor type level

17. New biomarker typesand
genomic signatures
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• TSO-500 genes, fusions and more
• Genomic signatures including but
not limited to:
o TMB
o MSI
o PD-L1
o PMSA
• Combination biomarkers
o BRAF negative findings
• Gene impact
o BRAF Activating
o Loss/Gain of Function

18. New drug interpretations
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• Detailed drug descriptions
o Commercial label- “Keytruda"
o Mechanism of action- “Anti PD-1"
o Status- "Approved" vs "Investigational"
o Indications for use- "Solid Tumors with MSI-high"
o Drug Class- "Immune Checkpoint inhibitor"
• Lists available clinical trials

19. New Report Templates
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• New somatic report templates
include:
o Report MSI, TMB
o Other Genomic Signatures
o Structural variants
o Negative findings
Put template
screenshot
here

20. Example Biomarkers
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• Colorectal cancer sample:
o MSH6 LOF
o Gene Signature: TMB High
o Gene signature: MSI High
o BRAF/KRAS negative finding – colorectal
Put variants to
evaluate
screenshot
here?

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Product Demo

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 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. eBook Update: Clinical Variant Analysis for Cancer
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Want a free copy? Request one in the questions or chat panel and
our team will follow up with you!

25. Innovation Awards
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The 2023 Golden Helix Innovation Awards will run from Dec. 1st, 2022 - Feb. 28th, 2023
• We want to see how YOU are using our tools to the best of their ability.
• Anyone using Golden Helix Software tools is eligible to submit for entry, and no prior publication of
research is required.
• Submissions can be for clinical or hospital laboratory work, academic research, government, or
commercial, we just want to see great examples of your workflows.
• 3 winners, each receiving 1 user license for either SVS or VarSeq, and first place receiving in addition
a Dell Latitude 5000 series laptop.
• All winners will receive the opportunity to present their research via webcast.
Goldenhelix.com/events/Innovation_Awards

26. Awards
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