VarSeq: Making Variant Discovery and Gene Panels Easy

Last week, our CEO Andreas Scherer announced our entrance into the clinical testing market with VarSeq. This week, I will be giving a webcast on Wednesday introducing this new tool and demonstrating its capabilities. (Register for the webcast)

VarSeq’s focused purpose is making NGS gene testing and variant discovery efficient, scalable and accessible to users with a broad range of backgrounds and specialties.

In this blog post, we will examine the use cases that VarSeq supports in more detail, but first I want to place this product launch in the context of Golden Helix’s own evolution as well as the adoption of this technology in our industry.

Although VarSeq is entering a market which has existing solutions, Golden Helix’s years of experience gives VarSeq the advantage of the deepest technological roots.

Doing the Hard things First 

We at Golden Helix have a track record of tackling the hard problems that can be solved with serious algorithm development (recursive partitioningCNV calling on the GPU, NGS collapsing methods with novel adjustments for sample relatedness). Our approach is to pay attention to the details and iterate relentlessly with our users through a support process that is integrated with product development.

While the popular approach of most NGS interpretation companies in this field is to wrap a bunch of open source academic command line tools through a shiny web interface, we often find that to provide our users with the best analysis and support we must become experts in algorithms and data sources ourselves and own the responsibility and often the code of the full stack of technologies we build into a product.

If you follow this blog, you will have seen many examples of this approach, where we have:

Whether you Write Grants or Build Tests, We Work for You

We love serving the research market. Our customers are doing amazing things and publish prolifically. We also see the line between research and clinic utility being crossed in both directions as the immediate impact of the knowledge generated by inspecting genomes meets the often relentless and heroic search families go through to end a diagnostic odyssey.

We feel the time is right for our core technology to be packaged in a tool that focuses on building a validated and repeatable workflow around variant discovery and gene testing.

This allows both researchers and those doing test development and execution to set up analysis workflows that meet their own needs, and run those many steps efficiently and without chance of human error over new samples again and again.

Oncogene Panels, Hereditary and Carrier Screening and Constitutional Disorders 

Ion Torrent Cancer Hotspot V2 filtered with an investigation of an intermediate result.

Ion Torrent Cancer Hotspot in VarSeq

Oncogene testing has already proven to be cost-effective and clinically impactful. We have been working with stakeholders running clinical labs to nail down a set of core features to support a test-oriented workflow.

These include:

  • Importing variants with the allelic frequency (ratio of somatic mutations to total) computed in batches of samples that were sequenced together
  • Annotating against hotspot and gene panel oriented tracks, as well as public data sources such as COSMIC, dbSNP and germline variant population catalogs.
  • Filtering using pre-defined presets tuned to the sample prep and sequencing process to remove germline, low quality or variants of little clinical significance.
  • Gene level views (with variant details) to support the process of writing up lab reports

While this list may sound like basic informatics, what has not been done is to place all of this in a fast, local, flexible and intuitive interface that can serve both the specialists building the tests and the technicians who implement it.

Very similar in their workflow requirements are gene tests for hereditary risk (such as BRCA1&2), carrier screening (such as cystic fibrosis) and constitutional and developmental disorders. VarSeq is equally capable of being the analysis engine for these tests.

Building on Strength: Variant Discovery 

VarSeq builds upon experience and core technology we have matured in our SNP and Variant Suite (SVS) flagship product to deliver the empowering experience that is the signature of our work at Golden Helix.

Trio analysis workflow looking at three dominant and two recessive inheritance patterns in VarSeq taking an input of over 2 million variants down to 36.

Trio analysis workflow looking at different inheritance models in tandem.

SVS supports variant discovery on NGS data, and has expanded to support many research goals, including exome trio analysis. Our SVS users love the power and flexibility of our data management affords. Often empowering them to do things only their bioinformatician peers would otherwise dream of.

But even researchers find themselves settling on their own best practices and wanting to repeat a series of steps on each new set of samples they analyze.

We wanted to enable beginners and expert users alike to start with sample variant calls, select an appropriate default or custom workflow and get to a list of well annotated candidate variants to start their investigation.

These steps include:

  • Importing variants with family relationships specified
  • Annotating variants against transcripts (similar to snpEff or Ensemble VEP), public frequency databases and functional predictions
  • Running complex filtering to automatically provide candidate variants in different inheritance patterns, such as de Novo dominant, inherited dominant and homozygous or compound heterozygous recessive.

Making it Easy to Get Started, Easy to Share

The design goal of VarSeq was to make these workflows easy.

With the help of many stakeholders who helped us validate and refine our design, and of course the full force of the Golden Helix development team that brought you SVS and GenomeBrowse, I believe we have achieved these goals.

With GenomeBrowse, we have learned that viewing and investigating existing data is a common denominator across all types of users and usually the starting point to for people starting their own analysis. We understand that science and medicine does not occur in isolation and that collaboration is central to each field’s mission.

For this reason, and to enable licensed VarSeq users to share their results in the most convenient way possible, VarSeq will always be free as a viewer of existing projects.

This means you can download VarSeq, register, and immediately open and explore existing projects like the ones highlighted by the screenshots in this blog post for free. The full power of GenomeBrowse visualization, the ability to see any step of the filtering process and the flexibility to export any of the resulting tables are all available.

VarSeq will be available for a yearly subscription with support which will allow a user, lab, or institution to choose the number of licenses needed in their environment. We have found this business model aligns our interests with yours, and provides the certainty to your cost planning regardless of the number of samples you may analyze.

Be sure to register for the live webcast this Wednesday to see VarSeq in action. We will also be announcing early mover promotions and our plans for ASHG and the public release that will soon follow.

Hope to see you there!

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