HyperDesign Online Software Tool

For Research Use Only. Not for use in diagnostic procedures.
Thumbnail image showing the HyperDesign Tool interface on a computer screen
User-friendly online probe design with HyperDesign Tool

Generating custom probe pools for targeted enrichment of next-generation sequencing libraries can be a daunting endeavor. Many traditional design tools are clunky, rely on poorly optimized design algorithms, or lack the support of a live person with years of design experience—leaving you wondering if you have the best design to capture your specific regions of interest. 

Roche's new online design tool, HyperDesign, is here to address those concerns. 

HyperDesign Tool is a user-friendly online probe design tool that takes advantage of Roche's two decades of in silico probe design experience. HyperDesign Tool's proprietary design algorithm has been optimized to achieve deeper and more uniform downstream sequencing coverage with fewer sequencing reads—even for difficult-to-capture regions. 

Comparison of HyperDesign Tool with design tools or services from other vendors

Generating custom probe panels can be a daunting task. While there are some online design tools that can help, many of these are clunky, rely on poorly optimized algorithms, or require contacting an expert designer–increasing turn-around time.

Our online, self-guided HyperDesign Tool overcomes these challenges, enabling anyone to generate panel designs on their own.

See the table below and watch the video on this page to get started on www.hyperdesign.com

HyperDesign comparison tool chart

Get started with a new design

Visit www.HyperDesign.com, log in* to your homepage, click on "new design," and follow these 4 simple steps ...

  1. Select your organism of interest and name your design.
  2. Add your targets by uploading gene names, bed files or genomic coordinates; or choose from a broad list of commonly used gene identifiers.
  3. Fine-tune your inputs, review your targets, and confirm your results.
  4. Submit your design for selection.

    ..then let our advanced algorithm do the work

    Once probe selection is complete, you’ll be able review the coverage results across your target regions.

    *If you were a registered user of our prior online design resource, NimbleDesign, your login name, and password have been transferred to HyperDesign Tool. Use these to gain immediate access.

Design your custom panel 

HyperDesign Tool

To place an order or ask a question:

The HyperDesign Tool replaces NimbleDesign.

Case Studies

Case Study #1. Fast and easy design of a custom target enrichment panel using the self-guided HyperDesign Online Software Tool

Read this case study to learn how HyperDesign Tool enabled a researcher to create target enrichment panels without any need for optimization and customization. The design request took only ~15 minutes to enter, and the resulting panel design file was received within an hour of submission without requiring additional adjustments—enabling the panel and accessory reagents to be ordered right away. The resulting probe panel (ordered from Roche) yielded excellent sequencing results–confirming that the HyperDesign Tool is a fast, powerful, and accurate method for designing custom NGS panels.

View the case study

Case Study #2. Streamlining next-generation sequencing probe panel design using the self-guided HyperDesign Online Software Tool

Designing a custom target-enrichment panel can be a time-consuming and challenging task. That is why Roche has designed HyperDesign Tool to make it quick and easy for any novice or experienced user to generate new designs, or to alter existing catalog or custom panels. The pre-balancing built into the proprietary algorithms of the cloud-based software platform helps users to quickly design panels without a need for further optimization. This study highlights a solution that leverages the self-guided HyperDesign Online Tool plus the streamlined KAPA library preparation and target enrichment workflows to deliver precise and uniform sequencing results.

View the case study

Case Study #1. A success story: Fast and easy design of a custom target enrichment panel using the self-guided HyperDesign Tool
Boshen Gao, M.Sc., Senior Application Scientist

“ I was impressed by how the HyperDesign Tool was able to help me create a robust probe panel design without a need for optimization, and that the subsequent sequencing results confirmed the expected performance of the panel.”

Highlights:

  • Creating a new panel design for ~50 genes associated with CRC was fast and easy with the free online self-guided HyperDesign Tool—even for a user with no previous design experience.
  • The design request took only ~15 minutes to enter, and the resulting panel design file was received within an hour of submission without requiring additional adjustments—enabling the panel and accessory reagents to be ordered right away.
  • The resulting probe panel (ordered from Roche) yielded excellent sequencing results—confirming that the HyperDesign Tool is a fast, powerful, and accurate method for designing custom NGS panels.

Goal of the panel design

Colorectal cancers are the second leading cause of cancer deaths both worldwide and in the U.S. impacting people as young as their 20’s(1). Thus, it is essential that oncology researchers have access to tools that will help with early identification of tumors. While a large number of CRC susceptibility genes and variants are known, many DNA sequencing workflows capture much larger regions of the genome—driving up sequencing costs, slowing down analysis, and requiring large amounts of data storage. A more efficient approach to sequencing CRC-associated regions is to focus sequencing reads on only the desired genomic regions through target-enriched NGS.

Boshen Gao M.Sc., a Roche Applications Scientist, recognized the need for a more focused CRC panel, and decided to design one using Roche’s self-guided online HyperDesign Tool. Boshen did not have any previous design experience prior to this experiment.

The design process and experience

After logging into the online web-based interface and naming his design, Boshen uploaded a .BED file containing the genomic coordinates of 50 genes related to CRC. The target region included both coding and non-coding regions, for a total target sequence size of ~4.7 kbp. Other parameters are shown in Table 1. The entire design process took about 15 minutes. 

Step by step instructions for the HyperDesign Online Tool design process:

  1. Log into HyperDesign.com and follow the prompts

  2. Submit your design for probe panel creation

  3. Once your panel results are returned (typically in ~1 hour), review the coverage results across your target regions and approve in HyperDesign.com

  4. Once your receive the confirmation email, order the probes and the required reagents; these are both provided in the confirmation email, enabling you to get started right away
Enjoy a more user-friendly experience with Roche's HyperDesign tool

Receiving the design files

In less than an hour, Boshen received a confirmation email notifying him that the design process was complete. He did not have to adjust his request parameters, received no vague error messages from HyperDesign Tool, and did not need to speak directly to a design scientist. This contrasts with design tools he tested from other vendors, which either took much longer, yielded numerous unclear error messages that had to be addressed, or were not capable of designing the required panel with desired sequencing metrics.

The final target enrichment panel design provided an estimated coverage of ~4.3 kbp, or 92.09% of the desired target sequences. This was an expected result, as the target region supplied to HyperDesign tool included challenging-to-design non-coding regions, which are known to contain repetitive elements. Designs from other vendors did not yield satisfactory projected sequencing metrics. 

The confirmation email from HyperDesign Online Tool also provided a list of reagents that were needed to set up the NGS hybrid capture reactions. Therefore, Boshen was able to go ahead and order the probes and the associated reagents after receiving the HyperDesign confirmation email.

Panel performance

When the probe panel arrived Boshen tested it with both gDNA and cfDNA samples, following the provided Instructions for Use to set up a hybrid capture reaction using KAPA HyperCap Workflow reagents. Sequencing results from the very first experiment, using both sample types, yielded ample sequencing reads and low error rates. Subsequent analysis showed excellent fold-80 penalty, on-target rate, coverage depth, and uniformity (Table 1). The fold-80 penalty from this panel design was ~1.5, which shows great uniformity.

Taken together, this case study demonstrates that someone who needs a custom target enrichment panel but has little to no design experience can easily use the self-guided Roche HyperDesign Online Tool to design a high-quality panel, enabling significant savings of both time and lab resources.

Sequencing result

80%+ coverage was expected due to this being a human DNA panel, with some repetitive regions that are expected to have low coverage. Panel coverage exceeded the expectation at 92%.

 

Metrics  
On-target rate 78-83%
Median coverage depth
78-99X
>30X coverage
70-91%
Fold-80 penalty
1.4-1.5

Table 1- Sequencing metrics for Roche CRC panel design with Roche HyperDesign Tool. Only cfDNA  data is shown here. gDNA data was comparable.

In summary, a novel colorectal cancer target enrichment panel was generated using Roche’s HyperDesign Tool, and achieved excellent estimated coverage without modification to default design parameters on the first trial. The panel design outperformed all other panel designs that were tried out from other vendors.

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Case Study #2. A success story: Streamlining next-generation sequencing probe panel design

Researchers at Roche were working on a project which involved designing a colorectal cancer research (CRC) panel for analyzing a set of 50 genes to identify key variants influencing disease progression and treatment response. 

An NGS target enrichment workflow may include target enrichment panel design. The steps of a panel design steps include: (1) Selecting target genes or regions of interest; (2) Fine-tuning the inputs; and (3) Submitting the design request. In this study, a custom target-enrichment panel for 50 genes related to CRC was designed using the HyperDesign Online Tool. To test the performance of this custom panel, sequencing libraries were generated using human gDNA and the latest KAPA Library Prep and Target Enrichment Kits.

HD-Probes-Performance-Comparison

The Challenge:

A challenging part of the project was the complexity of the design process itself–especially for the lab member running the project, who did not haveany prior experience in NGS target enrichment panel development.

The Solution:

The researcher in charge of the project, Boshen Gao, M.Sc. turned to the Roche HyperDesign Online Tool. This self-guided, cloud-based platform offered an intuitive workflow for designing custom target-enrichment panels. Boshen was able to quickly input the 50 target genes of interest, including challenging intronic regions known to harbor important variants. The HyperDesign Tool's pre-balancing algorithms streamlined the design process, eliminating any need for subsequent optimization

To complete the workflow, Boshen received an email within an hour that listed all of the needed probes and reagents to order, with their associated catalog numbers.  KAPA EvoPrep Library Prep Kit and the KAPA HyperCap Workflow were then used to prepare the target-enriched libraries.

The Results:

The HyperDesign Online Tool delivered a high-quality panel design in the first iteration. The key highlights included:

  • Efficient design: The HyperDesign Online Tool significantly reduced the time and effort required for panel design compared to other tools and services from other vendors.

  • Superior coverage uniformity: The resulting 4.3 Mb panel exhibited a Fold 80 penalty score of ~1.3, demonstrating excellent coverage uniformity. This meant that sequencing reads were more evenly distributed across the target regions, ensuring that all areas of interest were adequately covered.

  • High target coverage: The panel designed with the HyperDesign Online Tool, when combined with Roche probes, demonstrated a higher percentage of target bases covered at greater than 30X coverage, compared to panels designed with other vendor tools.

  • Efficient sequencing: The Roche solution prevented excessive sequencing of certain regions at the expense of others, ensuring that sequencing resources were used efficiently to generate meaningful data.

The coverage uniformity of the Roche panel, designed with HyperDesign Online Tool, was superior

Figure 1. Superior coverage uniformity for the Roche panel due to better design by HyperDesign Online Tool.
Mean % target baseses covered at >30x

Figure 1. Superior coverage uniformity for the Roche panel due to better design by HyperDesign Online Tool. The lower Fold 80 base penalty and higher % bases covered at or higher than 30X demonstrate superior performance of HyperDesign Tool and Roche probes.

Uniformly cover what matters for your research with the HyperDesign Online Tool

Figure 2. Minimize excessive coverage of some regions to achieve required coverage of all targets.

Figure 2. Minimize excessive coverage of some regions to achieve required coverage of all targets. Sequencing reads are distributed more evenly across the entire target region with the Roche probes. Probes from other vendors result in more regions being sequenced at excessively greater depth (>300-500X) than what is required. This means that these reads are not providing meaningful data, while other regions are being covered with less depth.

Conclusion:

For the researchers at Roche, the HyperDesign Online Tool–combined with Roche’s high-quality double stranded probes and the KAPA library preparation and target enrichment workflows–has proven to be a powerful solution for overcoming the challenges of an NGS panel design. The tool's ease of use and self-guided design, along with pre-optimized algorithms, were particularly beneficial. Thus, this tool can enable even those with limited prior panel design experience to create high-quality panels on the first try.

Read the Tech Spotlight to learn more about the superior performance of HyperDesign Tool and resulting Roche probes and library prep and target enrichment workflows compared to other design tools and probes from other vendors.

  1. Chen J. et al. Cause of death among patients with colorectal cancer: a population-based study in the United States. Aging (Albany NY). 2020 Nov 28;12(22):22927-22948.

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