DeciBio Insights

NanoString poised to make a play in clinical sequencing with Hyb & Seq

Research Tools

Hollywood, FL – Exciting times are upon us again at AGBT with multiple announcements from life science research tools players. For years now, people have been talking about the importance of long reads, and recently, we highlighted the progress made by Oxford Nanopore in this space. A year after debuting proof-of-concept data for Hyb & Seq, NanoString unveiled updated capabilities of the technology at AGBT in 2 hour-long lunch workshop to an eager audience. We got an up-close demonstration of the platform’s capabilities, and were impressed by the progress that NanoString had made in just a year, primarily revamping their chemistry. “We want to make the simplest to use sequencer in the world”, said Joe Beechem at the beginning of the workshop. It seems like they may be able to deliver on this promise. The company pulled a fun and successful stunt, and sequenced a cancer sample (lymphoid tissue) during the workshop, with the help of James Hadfield. The workflow can be seen in the slide below, provided by Joe.

 

Interestingly, the current configuration used a modified version of the nCounter SPRINT. As a result, both gene expression and sequencing could be run on the same platform at the same time, which positions NanoString to address many of the interesting biomarker questions in the red-hot field of immuno-oncology (e.g., immune repertoire analysis or tumor mutation burden in conjunction with gene expression)*.

The technology is based on NanoString’s molecular barcoding chemistry. It has proven very robust, especially when analyzing FFPE samples, which can have degraded DNA and RNA (less likely to be amenable for sequencing by synthesis approaches vs. hybridization-based approaches).

Here are some of the key highlights of the platform (Additional information on the presentation and technology can be found on James Hadfield’s and Dale Yuzuki’s blog entries):

  • Hyb-Seq is an hybridization-based platform that currently runs on a modified SPRINT nCounter.
  • The technology requires no enzymes, amplification, or library preparation
  • It uses 6-mer hybridization probes similar to the old chemistry, but that have been miniaturized from 2,000 nm to 20-50 nm in length**
  • It enables 20M reads, of both long and short fragments; to date, the longest fragment analyzed was 33 kb, with long-range phased haplotypes resolved naturally due to chemistry design
  • Accuracy depends on base coverage with single-molecule single pass QV14 (96% accuracy),and QV’s increasing to 22, 27, 31, 40 (~99.99% accuracy) for a base coverage of 2,3,4, 5, respectively. That level of coverage will be obtained in less than ½ of a day for a 100 gene cancer panel
  • Both DNA and RNA can be analyzed on the same run
  • The platform will be geared for the clinical market, and offer targeted panels (120 gene panel demonstrated in the workshop) that can be run from an FFPE sample to sequencing data in an impressive <1 hour (from FFPE-curl) with less than 15 minutes of hands-on-time! In the near future, the company expect to be running 10-1,000 gene panels.

Hyb & Seq’s throughput (targeted panels, with no goals to go broader at this point), simplified workflow, and rapid turn-around-time make it well-suited for clinical applications, a segment NanoString already plays in with their Prosigna breast cancer assay. A key application will include targeted oncology panels (which ties to the company’s focus/expertise), which is one of the most attractive segments of the clinical sequencing market, but also one starting to be crowded by Illumina, Ion Torrent, and most recently Qiagen. It will be interesting to see how NanoString decides to position the platform. They may decide to go after decentralized hospitals, in a move akin to Qiagen (which placed 55-60 sequencing instruments in 2016) or Genia (which we apparently won’t hear more about at this conference). These customers may be price sensitive, so we expect adoption to be largely driven by cost / reimbursement.

We talked with a few workshop attendees, and feedback was positive. Comments included:

  • “I would want to know how much they can scale it, in terms of panel size, and what will be the cost of the box and per assay.”
  • “We have a nCounter now and it works really well for gene expression of FFPE samples. So I would expect that NanoString can pull it off!”
  • “It’s cool but it’s a long way off! A lot of people announce having a beta coming in 2 years.”
  • “We need clear clinical applications for these novel sequencing tools. How is data from this instrument looking a long reads DNA and RNA going to help my patients?”
  • “It takes me 8 weeks to get a BL-2 certification in Boston – I’m impressed that they set this up in a week in Florida!”
  • “Show me the raw data!”
  • “Addressing bottlenecks in library prep to get to results in 1 hour could really move the field forward.”

NanoString continues to perform strongly and, given their history of innovation and prior success with the nCounter systems, we expect that Hyb & Seq could be competitive in a few years. Additionally, the reputation of their robust technology and existing platform placements could facilitate adoption. We’re excited about this technology and await further developments. The platform may be available as a beta-instrument in 2019, with the full chemistry ready by AGBT 2018.

* NanoString has also been developing multi-analyte or “3D biology” applications, allowing researchers to profile DNA, RNA, and proteins from the same sample to generate maximal insights from limited sample, another attractive feature. They have also been working on and presenting here in a poster a digital spatial profiler (DSP) for optical barcodes resolved on tissue (50 proteins and 100 RNAs).

** Interestingly, NanoString can add longer oligos if the regions of interests have homopolymers longer than 6 base pairs.

DeciBio is a strategy consulting and market intelligence firm focused on clinical diagnostics and life science research tools. Learn more about our services and products, or send us an email at [email protected].

 

Author: Stephane Budel, Partner at DeciBio Consulting, LLC
Co-Author: Miguel Edwards, Sr. Associate at DeciBio Consulting, LLC
Co-Author: Andrew Aijian, Project Leader at DeciBio Consulting, LLC
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