Somatic analysis is a complex and precise process that is constantly evolving. As the volume of available data and the accessibility of sequencing technology increase, so too does the value of a versatile, well-vetted, and efficient workflow solution. In this webcast, we will take a deep dive into the current state of our AMP interpretation software and explore various ways to optimize workflows. For anyone from grizzled VarSeq veterans to those seeing our software for the first time and labs of any size, we will provide a practical overview of our somatic analysis capabilities and how those capabilities scale with improving technology. Throughout this webcast we will be discussing the following: - Universal principles of somatic workflows, providing baseline recommendations - Specific tumor-normal and somatic-only use cases - VSClinical AMP interpretation hub and some variants of interest - Opportunities for automation and how to decrease time to report for increased throughput Join us as we show off the versatility and scalability of our AMP interpretation capabilities!

1. User perspective for somatic variant
analysis in VSClinical AMP
8/10/22
Presented by Solomon Reinman, Technical FAS

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3. User perspective for somatic variant
analysis in VSClinical AMP
8/10/22
Presented by Solomon Reinman, Technical FAS

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?
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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. When you choose Golden Helix, you receive
more than just the software
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Software is Vetted
• 20,000+ users at 400+ organizations
• Quality & feedback
Simple, Subscription-
Based Business Model
• Yearly fee
• Unlimited training & support
Deeply Engrained in Scientific
Community
• Give back to the community
• Contribute content and support
Innovative Software Solutions
• Cited in 1,000s of publications
• Recipient of numerous NIH grant and other
funding bodies

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10. AMP Guidelines Overview
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• Somatic analysis
using VarSeq’s AMP guidelines
• Workflow design and
evaluation process
• Customized reporting

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Poll Question: What kind of somatic
analysis are you performing?
Research or clinical (per-sample)?

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VSClinical - AMP Guidelines
• Biomarker Definition
- Biological states with indications for
treatments, prognostic, or diagnostic
outcomes
- Presence or absence of proteins,
antigens, and specific genomic
attributes of the tumor
• Common Cancer Biomarkers
- HER2+: High levels of HER2 receptor
protein
- MSI-H: Microsatellite instability-high
- BRAFV600E: Activating mutation V600E
- ERBB2Amp: Amplification of ERBB2
- BCR-ABL1: Activation of ABL1 with
BCR fusion
- TP53WT: No significant alterations of
critical TSG
Tier I: Variants
of Strong
Clinical
Significance
Therapeutic,
prognostic &
diagnostic
Level A Evidence
FDA-approved
therapy
Included in
professional
guidelines
Level B Evidence
Well-powered studies
with consensus from
experts in the field
Tier II: Variants
of Potential
Clinical
Significance
Therapeutic,
prognostic &
diagnostic
Level C Evidence
FDA-approved
therapy for different
tumor types or
investigational
therapies
Multiple small
published studies
with some consensus
Level D Evidence
Preclinical trials or a
few case reports
without consensus
Tier III: Variants
of Unknown
Clinical
Significance
Not observed at a
significant allele
frequency in the
general or specific
subpopulation
database, or pan-
cancer or tumor-
specific variant
database
No convincing
published evidence
of cancer association
Tier IV: Benign
or Likely Benign
Variants
Observed at a
significant allele
frequency in the
general or specific
subpopulation
databases
No existing published
evidence of cancer
association
(2017) Standards and Guidelines for the Interpretation and Reportingof Sequence Variants in Cancer:

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Golden Helix – CancerKB
• Cancer Interpretation Catalog
- Included with AMP Guidelines
• Primary Values
- Curated by professionals in the clinical context
- Jump starts interpretation
- Accelerates time to reporting

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VSClinical – Clinical Report
• VSClinical conducts the clinical variant analysis
based on ACMG and AMP guidelines
- Automated population of the clinical report-based
workflow outcome
- Standardizing of variant level interpretation based on
customizable assessment catalogs
- For somatic variants, GHI provides predefined clinical
assessments via our CancerKB catalog
• Rendering of clinical reports within seconds
• Supported output formats
- Word
- PDF

16. VarSeq somatic analysis scales
from gene panels to WGS
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• Users are accustomed to somatic variant analysis
using gene panels
• Industry is trending toward whole-exome and
whole-genome sequencing
• Pipeline automation and large-scale processing
make VarSeq the perfect tool for scalability
• Check out our last webcast for details on how these
features can maximize profitability in your lab

17. Panels, Exomes, and WGS
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References of VarSeq use cases
Germline variants in DNA repair genes are associated
with young-onset head and neck cancer, Santiloni Cury
et al., 2021
Personalised virtual gene panels reduce interpretation
workload and maintain diagnostic rates of proband-only
clinical exome sequencing for rare disorders, Molina-
Ramírez et al., 2021
Whole genome sequencing identifies rare genetic
variants in familial pancreatic cancer patients, Tan et al.,
2022

18. VarSeq Demo
• Single somatic sample
workflow
• Example variant: obvious
oncogenic BRAF V600E for
Melanoma
• Simple examples of report
customizations
• Tumor-normal workflow
• Highlighting filter design
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Product Demo

20. NIH Grant Funding Acknowledgments
20
• 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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22. T-Shirt Competition
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• First Place: $300
• Second Place: $200
• Third Place: $100
• Draw it out or write it down!
• Visit GoldenHelix.com/forms/event/t-shirt-
competition by September 14th.
• Winners will be notified by September 21st.
• T-shirts will be unveiled at ACMG 2023

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