The automation of clinical NGS workflows provides a number of important benefits for labs. Automation reduces the time required to produce a clinical report, mitigates the possibility of human error, and improves the precision of clinical results. In turn, these benefits create higher profitability from a P&L perspective. Golden Helix software is designed to meet these needs by automating the full analysis workflow from sequencer to clinical report on a fixed annual subscription model. We are looking forward to discussing the best practices of maximizing profitability in your NGS testing lab and how Golden Helix supports these efforts. Join us in this webinar as we cover how to develop repeatable cancer and germline interpretation workflows that scale from panels to whole exomes and genomes.

1. Maximizing Profitability in Your
NGS Testing Lab
Develop repeatable cancer and germline interpretation workflows that scale
from panels to whole exomes and genomes
Dr. Andreas Scherer, President and CEO of Golden Helix
Gabe Rudy, VP of Product & Engineering

2. NIH Grant Funding Acknowledgments
2
• 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/STTR Matching Funds Program Grant 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.

3. Who Are We?
3
Golden Helix is a global bioinformatics company founded in 1998
Filtering and Annotation
ACMG & AMP Guidelines
Clinical Reports
CNV Analysis
Pipeline: Run Workflows
CNV Analysis
GWAS | Genomic Prediction
Large-N Population Studies
RNA-Seq
Large-N CNV-Analysis
Variant Warehouse
Centralized Annotations
Hosted Reports
Sharing and Integration

4. Golden Helix named on the
2019, 2020 & 2021 Inc. 5000 list
Our track record is profitable growth!
4

5. Cited in 1,000s of Peer-Reviewed Publications
5

6. Over 400 Customers Globally
6

7. When you choose Golden Helix, you receive
more than just the software
7
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

8. Precision
Medicine
• The field of Medicine is rapidly changing towards
a data driven and analytical approach to
diagnostics and treatment selection.
• Leveraging Genetic Information is in the center of
this development as it gives clinicians the ability
to tailor treatment options specific to the
molecular profile of a patient.
• How do we do this profitably?

9. A key enabler: lower sequencing cost per genome
9
$46,774
$20,963
$7,666
$5,671
$4,008 $3,970
$1,176 $1,015 $1,232 $1,039 $645
$0
$5,000
$10,000
$15,000
$20,000
$25,000
$30,000
$35,000
$40,000
$45,000
$50,000
2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
Cost per Genome
As the cost per genome declines, the use of NGS-based testing will become the standard across hospitals globally. According to Grand View Research,
the global bioinformatics market was valued at US $4.62 billion in 2015. It is estimated to grow to about 14 billion by 2024.

10. 10
Regulatory Landscape Reimbursement
Testing Technology Physician Adoption
Bioinformatics
Consumer Demand
Early Adoption Moderate Adoption High Adoption
Market focus is on science and
research, lack of infrastructure,
clinical evidence and physician
education.
Clinical genetic standard for selected
targets and therapeutic areas.
Bioinformatics increasingly crucial for
diagnosis and treatment selection.
Greater availability of data
around testing with genetic
services becoming standard of
care for a majority of patients.
NGS Testing Adoption Curve

11. Next-Gen Sequencing Market
11
Next-Generation Sequencing (NGS) Market
Global Forecast to 2026, Markets and Markets 2021

12. NGS Market by Application
12
Next-Generation Sequencing (NGS) Market
Global Forecast to 2026, Markets and Markets 2021

13. NGS Market by End User
13
Next-Generation Sequencing (NGS) Market
Global Forecast to 2026, Markets and Markets 2021

14. NGS Market by Application
14
Next-Generation Sequencing (NGS) Market
Global Forecast to 2026, Markets and Markets 2021

15. Market Summary
15
Next-Generation Sequencing (NGS) Market
Global Forecast to 2026, Markets and Markets 2021

16. Today’s Reality for NGS testing labs
16
• Multiple vendors
• Homegrown pipelines
• Increased support costs in a multi-platform environment
• High touch workflows
• Reimbursement issues
• Third party participating in your revenue stream
Never ending increase of
workload
Fast changing
testing market
Experts are tough to come
by
Tactical Issues

17. Key to Profitability
17
The core tenants of long-term success
Ability to create new tests
quickly according to
market demand
Bottom line-oriented
business partners enabling
your lab
Scalable solutions and a
high degree of automation

18. Ability to Rapidly Develop New Tests
18
Small Startup Lab
A few hundred tests
per year
Regional Lab
5-10,000+ exomes
per year
National Genome Center
10,000s whole genomes
per year
Gene panels to exomes to whole genomes
Cancer and Hereditary Disease Tests
Flexible Reporting Options

19. 19
• Local-first algorithm and data strategy
• Building from-scratch algorithms and
integrated data storage strategies
• FASTQ to clinical reporting in one solution,
with training and support
• Industry standard guidelines:
o ACMG: Germline interpretation for
diagnosis and hereditary disease risk
o AMP: Somatic interpretation for targeted
molecular therapy and cancer prognostics
• Automation and customization of lab-
specific needs
• Long term data storage and knowledgebase
management with VSWarehouse
Bottom Line-Oriented Partners Enabling your Lab
Golden Helix Clinical Suite

20. 20
Hospital
Research
Clinic
Clinician Patient
Bills
Reimbursement
Medicaid
Insurer
Inhouse Pathology Labs
• Conduct all crucial elements of the pipeline work inhouse
Testing Labs
• Provide outsourcing services to Hospitals and Clinics
• Various service levels
Other Hospitals and Research Clinics
• Conduct the entire diagnostics process
GHI
Determines treatment
Pay license
fee
Enables
Clinical Report
funds
Bottom Line-Oriented Partners Enabling your Business
Flat Fee-Based Business Model

21. Scaling an NGS Lab Throughput
21
• Strategies to Manage Scaling Constraints
o Design around turn-around time
o Automate analysis
o Re-use of previous work
o Guided workflow decision support
o Lock down the workflow
Personnel
Compute
Turn-
Around
Time
Quality &
Data
Security
Scaling Constraints

22. Scaling Compute for NGS Analysis
22
• Automated workflow:
o Align & Call
o Annotate & Filter
• Interactive workflow:
o QC samples and variants
o Classify and interpret variants
o Review and report
• Warehouse and Data Lifecycle
o Compute resources
o Personnel
o Turn-around time
Seq
CNVs SVs
Variant
Annotate
Reads
Alignment
Annotate
Annotate
Filter Filter Filter
Interpret
Warehouse Report
Cohort
Analysis
Re-Analysis
C
Automated
Interactive
Long Lived

23. • Example NovaSeq Run (1 or 2 a week)
o 50 whole genomes or 500 exomes
o 5TB total storage /week
o 260TB total storage / year
• Data lifecycle policy required
o Move to archival (~10 years) such as tape
o Save inputs and outputs, re-create
intermediate
• Cloud storage costs generally exceed
on-premise
o Cost 1 Year S3 storage 260TB = $71,760
o Cost to download 260TB = $23,400
Scaling Storage for NGS Analysis

24. • Guided workflows gains
o Self-guided
o Reduce chance of errors
o Reproducible results
o Aggregators of knowledge
• Auto-apply previous interpretations
• QC improves over time, leverage cohort
• Clinical Trial Performance Evaluation
o Two clinical labs, in-production tests
o Manual vs Guided workflow
o Reduced turn-around time
o Reduction in errors / rework
Scaling Personnel
Reduced Time Reduced Rework
Site A 42% 96%
Site B 62% 100%
Manual Cancer Sample Workflow vs VarSeq Suite

25. • Quality & Data Security Increasingly Important:
o IVDR compliance rolling out over coming years
o Supplier evaluation: are they following ISO 13485
o Large investment in quality systems, validation
o Home-brewed solutions are entirely uneconomical
o Fewer multi-solution vendors rather than many single-
purpose vendors
• Quality Management System Constraints:
o Cost of change is high: longevity of vendor and support
o Vendor must support locked down workflows
o Updates/upgrades require re-validation, do on lab schedule
Scaling Quality & Data Security

26. Scaling Scenarios
26
• Region Testing Lab Scaling Exomes
• Scaled to hundreds of exomes a week
• Batch work must complete over the weekend
• Windows-centric IT infrastructure
• Pharmaceutical Services Co Scaling Genomes
• High volume, batch-oriented WGS processing
• Fully automated locked-down deliverables
• Docker-centric pipeline
• Nation-scale genome center
• High security requirements
• No outbound internet
• Groups with private workspaces

27. 27
• Prefers fewer large servers
• Target time limit of 24 hours to process 300 exomes
(buffer time for re-run if failure)
• Windows server with Powershell scripts
• Analysis workflow includes:
• Coverage stats and QC
• VS-CNV calling
• Annotation and filtering
• Gene panel and phenotype automation
Region Testing Lab Scaling Exomes

28. Pharma Services Scaling Genomes
28
• Deliverables are locked down through versioned
pipelines
• All steps inside read-only Docker containers
• VSPipeline + Annotations + Project Templates
• Local Linux cluster and cloud deployment scenarios
• Secure Cloud deployments in China with no
outbound internet access
• Batch node job:
• Download docker containers
• [Cloud only] Download BAM, VCF from storage
• Docker run pipeline
• [Cloud only] Upload results to storage

29. Genome Center Scaling Genome Interpretation
29
• Air-gapped environment with no direct internet
• Internally mirrored data and license servers
• Leverage Linux cluster for interactive analysis
• Segregated into groups
• Group level access to input/output files
• Group level permissions and sharing
• Group level VSWarehouse
• Aggregate and share across groups

30. Key to Profitability: Summary
30
The core tenants of long-term success
Establish the test portfolio
for your lab that your
customers are demanding
Ensure a profitable
operating model per test/
category
Scaling up test volume

31. Questions & Answers
31
Learn more about Golden Helix’s solutions
We would love to share more about how our end-
to-end solutions can be tailored for your lab’s
specific needs.
EMAIL US AT INFO@GOLDENHELIX.COM
We have a number of learning resources on our
site: eBooks, webcasts, case studies and more!
VISIT WWW.GOLDENHELIX.COM
Please enter your questions into the “Questions” pane
of your Zoom webinar platform. All questions will be
answered anonymously.

32. NIH Grant Funding Acknowledgments
32
• 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/STTR Matching Funds Program Grant 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.

33. 33
News & Publications

34. Questions & Answers
34
Learn more about Golden Helix’s solutions
We would love to share more about how our end-
to-end solutions can be tailored for your lab’s
specific needs.
EMAIL US AT INFO@GOLDENHELIX.COM
We have a number of learning resources on our
site: eBooks, webcasts, case studies and more!
VISIT WWW.GOLDENHELIX.COM
Please enter your questions into the “Questions” pane
of your Zoom webinar platform. All questions will be
answered anonymously.