As our users have come to know, VarSeq serves as a hub for variant annotation and the full interpretation/classification of germline (ACMG) and somatic (AMP) variants. Whether direct annotation or backend variant evidence is being presented to the user via VSClinical for the interpretation process, users greatly benefit from the hosted variant databases being available directly from VarSeq. Our team has automated much of the curation process and hosts the ongoing updates to these tracks so that users no longer suffer manual review of each database via the web or manual curation efforts. Useful databases include ClinVar and ClinGen for classification submissions, gnomAD exomes/genomes for filtering out common variants in the population, RefSeq for gene impact and sequence ontology assessment, and OMIM for phenotypic information. Obviously, there is a large collection of databases out there, and not all of them make it into our automated queue. However, GHI supports the utilization of custom databases in our software. This webcast will expose features of custom database curation/utilization in VarSeq to optimize your NGS workflows even further. During the presentation, we will discuss many different approaches with custom annotations, including: Interval Tracks: Bed files defining target regions for coverage calculations and CNV detection. Assessment catalogs: record keeping of variant classification/interpretations in VSClinical. Frequency catalogs: approaches to capture all variant allele frequencies at a project level and cohort level with VSWarehouse.

1. VarSeq Custom Database Curation
Capabilities
April 13, 2022
Presented by Darby Kammeraad, Director of Field Applications Services

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3. VarSeq Custom Database Curation
Capabilities
April 13, 2022
Presented by Darby Kammeraad, Director of Field Applications Services

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/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.

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
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

6. Cited in 1,000s of Peer-Reviewed Publications
6

7. Over 400 Customers Globally
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8. When you choose Golden Helix, you receive
more than just the software
8
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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11. Accessing Raw Variant Databases – Building your workflow
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• Curated Public databases
• Lock down version
• Notifications for track updates
• Premium Annotations:
- CADD
- COSMIC
- Conservation Scores
- SIFT/PolyPhen2
- Splice Site Algorithms
- OMIM phenotypes and Genes
- 1kG Phase3 Variant
Frequencies
- ClinVar
- CIViC
- dbNSFP Functional
Predictions
- dbSNP
- ExAC
- RefSeq Genes, NCBI
- ClinGen Dosage
Sensitivity Mapping

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Audience Poll
What types of internal databases are you leveraging in your next-gen sequencing pipeline? Choose
all that apply.
A. Bed files defining targeted panel
B. BioBank or cohort data with computed allele frequencies
C. Collection of variant classifications/interpretations following ACMG/AMP guidelines
D. Other

13. Automated Variant Classification
13
• Increased lab throughput
• Consistent results
• Shorten learning curve
• Staying abreast of new developments
Germline
Somatic

14. Backend Annotations – Automated Variant Classification
14

15. Backend Annotations – Automated Variant Classification
15

16. Backend Annotations – Automated Variant Classification
16

17. Leaving Door Open For Custom Annotations
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• Lock down version
• Notifications for track updates
• Premium Annotations:
- CADD
- COSMIC
- Conservation Scores
- SIFT/PolyPhen2
- Splice Site Algorithms
- OMIM phenotypes and Genes

18. Leaving Door Open
For Custom Annotations
18
• Lock down version
• Notifications for track
updates
• Premium Annotations:
- CADD
- COSMIC
- Conservation Scores
- SIFT/PolyPhen2
- Splice Site Algorithms
- OMIM phenotypes and Genes

19. Custom Curation Examples
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• Bed Files: Defining Targets for panel
• Calculate targeted gene coverage
• CNV detection
• Variant Tracks: Allele Frequencies
• Eliminate common variants and artifacts
• Variant Interpretations/Classifications
• Integrate previously evaluated variants into ACMG automated workflow in VSClinical

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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 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.

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Visit us at ESHG 2022
Booth 476, Hall X5
• Stop by for a talk with our CEO, Andreas, and VP of
Product and Engineering, Gabe, and Area Director
Dana
• Exhibitor Talk: Profitability of your NGS Lab

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