NEW YORK – NanoString Technologies has made good on plans to enable next-generation sequencing as a readout for its GeoMx spatial analysis platform.
Last week, the firm launched its new Cancer Transcriptome Atlas (CTA) panel, which covers 1,800 genes in 100 pathways critical to immunoncology research and can include up to 60 custom genes. As the first NGS-enabled GeoMx Digitial Spatial Profiling assay, it is the "single most important product launch in the company's history," NanoString CEO Brad Gray said during a conference call with investors on Monday following the release of the firm's second quarter financial results. "What we've come to learn is that spatial biology is the flip side of the coin to single-cell [analysis]," he later added. GeoMx, which had previously required a NanoString nCounter instrument, can now be placed upstream of nearly any Illumina sequencer, which vastly increases the reach of spatial biology, Gray said. Already, the firm is seeing a measurable effect on sales of GeoMx systems, with about half of the orders in the second quarter placed by customers intending to make NGS the primary readout.
Gray also announced a new partnership with Illumina to codevelop software that will allow researchers to analyze GeoMx data on Illumina's Dragen Bio-IT platform. "This partnership helps solve some important issues that could be faced by customers and helps reassure them that our technologies work seamlessly together," Gray said. Financial and other details of the partnership were not disclosed.
Several high-profile labs have already begun using the CTA to generate data. "It's an interesting bridge of functionality and worked great right out of the box," said Chris Mason, a researcher at Weill Cornell Medicine who has been using the immune system related content in the panel to analyze tissues from patients who died of COVID-19. Weill Cornell's pathology lab obtained a GeoMx instrument prior to the pandemic and Mason's team has added in several genes not normally found in the CTA which are relevant to the disease. "The data are really promising," he said, with an average of 800 to 1,000 genes detected across different tissues. Quality control experiments detected 1,783 probes out of 1,837, he added.
Other outfits who have picked up on NGS-enabled GeoMx include Aviv Regev's lab at the Broad Institute, cell therapy researcher Carl June of the University of Pennsylvania's Perelman School of Medicine, and Jim Heath of the Institute of Systems Biology, company officials said.
Demand for NGS
NanoString has been talking about spatial genomics as far back as 2016, Gray said in an interview, and the firm has been consistently surprised with customers' level of interest.
The company launched the GeoMx platform, which enables both protein and gene expression analysis using the nCounter platform in particular regions of interest as small as 32 micrometers across, in March 2019. By November of that year, NanoString announced plans for NGS readout, first in its technology access program and later as a kit. As of June 30 of this year, the installed base for GeoMx was 69 instruments.
Offering the CTA through its early-access program gave NanoString a preview of the demand for NGS-compatible assays. The company saw the volume of NGS projects increase "substantially" and it has grown to account for 60 percent of all new projects in the program, Gray said.
Where previously, existing customers had accounted for about 70 percent of sales, now, sales are split almost evenly between new and existing customers. Gray added he expects the percentage of customers new to NanoString to continue to grow. He also doesn't believe the move will cannibalize nCounter sales in the near term. In the second quarter, only about 20 percent of nCounter instruments were sold in GeoMx bundles, but even if nCounter sales decrease in the future, "the GeoMx opportunity so vastly outweighs the nCounter opportunity, it would be manageable in the overall context of the company," he said, adding that NGS consumables have nearly twice the price point of nCounter consumables.
Sequencing setup
The cancer panel fits easily into the sequencing workflow, Mason said, and uses standard Illumina library preparation. The ability to work with formalin-fixed, paraffin-embedded samples was absolutely necessary for his group due to its work with COVID-19 samples. Mason's team used the Illumina NextSeq platform, which was sufficient for its needs. "You don't have to go crazy deep on [the sequencing]," he said. "You don't need a NovaSeq run." The team got about 3,000 reads per gene on average, he said.
While the average number of genes per region of interest was 800 to 1,000, Mason warned that gene expression is as variable as the tissue type: some regions only yielded several hundred genes, while others yielded up to 1,500. The study looked at several dozen regions of interest and produced gene expression profiles similar to those seen in a bulk sequencing assay. "The cool thing I like most is the ability to deconvolute expression and protein levels and see the cell types present in different tissues," Mason said. "I could see infiltrating macrophages coming in and disrupting the lungs in COVID-19 patients … we could view the pathogenesis in a new light, or with higher granularity, at least."
While COVID-19 is fueling interest in GeoMx, NanoString reported that the pandemic environment has slowed shipments and installations, and Gray said the company would continue to experience a headwind for consumables sales as a result. On the bright side, Gray said the firm has managed to stick to its original release timeline for the follow-up Whole Transcriptome Atlas, which will have more than 18,000 probes and should be available through the early-access program by the end of the year and launched more broadly in 2021.
Gray added that the firm is working to adapt the readout of GeoMx protein assays to NGS using DNA-barcoded antibodies.
All this adds up to massive expectations for GeoMx. NanoString has previously touted a twentyfold increase in the addressable market for NGS-ready GeoMx, given the huge gulf in placements between Illumina sequencers and nCounter systems. But Gray suggested that NanoString had actually underestimated the opportunity in discovery research. "Interest in NGS has far exceeded our expectations," Gray said in an interview. "We're engaging with discovery researchers for the first time. It really speaks to the ability to cover a large number of genes. Engagement in our sales funnel has grown faster than we initially planned for."
Gray told investors that when the whole-transcriptome assay arrives, it will "allow us to appeal not just to cancer and immunology researchers we've engaged with in the past, but also to people working on any biological problem in human or mouse. And that starts to bring in nearly every researcher in the world."