10x Genomics has begun commercial shipments of a new 5,000–plex gene expression panel that increases plex by an order of magnitude over previous panels, a month after announcing the launch of the product—and four months after arch-rival NanoString Technologies, a Bruker Company, brought to market its own high-plex panel allowing researchers to measure 6,000+ RNA targets.
10x says its Xenium Prime 5K Pan-Tissue and Pathways panel features enhanced chemistry enabling the increase in the number of cells capable of being imaged compared with previous gene expression panels ranging from the company’s 247-gene mouse brain panel to the 379-gene mouse tissue atlassing panel.
“It has a lot of the content that people have asked for from our custom panels,” Ben Hindson, PhD, 10x’s co-founder and CSO, told GEN Edge. “It’s a nice panel in terms of pretty comprehensive coverage of the transcriptome, and it should also enable customers to just take their samples and get lots of really informative data after the run is complete.”
With 5,000 genes, the new panel is designed for comprehensive profiling of cell types and states and cell signaling pathways across multiple tissue and disease types, according to 10x. The panel can be customized with up to 100 additional genes, including isoforms, exogenous sequences such as guide RNAs (gRNAs) and barcodes, chimeric antigen receptor T-cell (CAR-T) transcripts, and viruses.
The breadth of the panel has attracted interest from potential customers within biopharma, as well as academic researchers specializing in single-cell research.
Covers 80% of requests
“I would say it covers about 80% of the requests that we’ve gotten from all those customers that we’ve worked with on either the tissue-specific or the disease-specific panel. It pretty well encompasses a lot of the most common requests, but it also offers customers customization for those who maybe feel that there’s something that’s not quite included that should be.”
What makes the other 20% of requests a no-go for adding to the panel? A combination of feedback from early-access customers and the utility value of the genes: “I would say that some genes aren’t that interesting, and they take up a lot of real estate and don’t give you as much information. So, we try to take those off the list per se, because they’re not very informative.”
The list price for Xenium Prime 5K is $7,500 for each slide. Each run is two slides, making the total cost per run $15,000 in the United States. Xenium Prime 5K also delivers improvements from previous panels that include enhanced per-gene sensitivity, improved specificity and spatial fidelity, integrated multimodal cell segmentation, a workflow compatible with both fresh frozen and FFPE samples—plus the ability to let researchers analyze up to 472 mm² of human or mouse tissue in six days or less—speed, and throughput that the company calls industry-leading.
While Xenium Prime 5K may feature fewer genes than NanoString’s panel, Hindson said 10x has focused heavily on the panel’s performance: “For the most part, we’re pleased with how those landed in terms of sensitivity, specificity, and throughput, together with in-line data analysis and data processing that’s happening while the instrument’s running, so when it’s done, you get your data and you go off and start analyzing.”
And while numerous research areas can benefit from the panel, Hindson said, the biggest potential opportunity for gleaning knowledge through Xenium Prime 5K is in oncology as researchers delve into the tumor microenvironment, looking at the single-cell resolution, how cells are programmed, how close they are to one another, and how they may interact with each other.
“I think there’s potential for new biomarkers based on the spatiality data as well. I think that’s why at conferences like AACR [the American Association for Cancer Research], there’s just a tremendous amount of excitement for looking at this high content, in situ data for studying the tumor microenvironment and then looking for potential new therapies, looking for why therapies may have worked in one patient and not in the other.”
10x formally announced the launch of the panel in late May, four months after co-founder and CEO Serge Saxonov, PhD, first announced Xenium Prime 5K among a series of product improvements planned for this year in January at J.P. Morgan’s 42nd Annual Healthcare Conference.
NanoString launches 6K panel
The following month at the annual Advances in Genome Biology and Technology (AGBT) 2024 conference in Orlando, FL, NanoString announced the launch and full commercial release of its CosMx™ Human 6K Discovery Panel, the first single-cell spatial panel enabling research scientists to measure over 6,000 RNA targets, representing nearly every human biological pathway.
“From the technical perspective, we pushed the envelope harder than anybody else by far,” Joe Beechem, PhD, NanoString’s CSO and senior vice president of research and development, told GEN in an exclusive interview from AGBT.
Human 6K enables analysis of 6,175 genes with 20 control targets, and the ability to customize up to 200 additional targets of interest.
“The applications that we built this panel for were very broad. We went after all of translational biology, with a strong focus on cancer, immunology, and neuroscience. Those are hallmarks for us here at NanoString, the biggest areas of translational research,” Erin Piazza, PhD, associate director of bioinformatics with NanoString, told GEN Edge recently. “But we also looked at many other applications things crossing all of physiology endocrinology and metabolism, cardiovascular disease, developmental biology. We cast a very broad net with this panel, with the hope that most researchers, especially in the translational space, would be able to take advantage of it.”
Beyond numbers
The more genes a panel can accommodate, the better for researchers, though Piazza added that NanoString’s approach goes beyond numbers:
“Researchers love plex. When offered panels of varying size, larger is almost always preferred because it reduces the concern that the researcher has missed important findings. It reveals deeper biological insights and conserves precious tissue samples,” Piazza said.
“While we are delivering to the market the highest plex panels available, our approach is more than sheer numbers,” she said. “Our value proposition to researchers is providing biologically curated high-plex data that meaningfully advances their understanding of a broad variety of translational and discovery research areas.”
NanoString says its approach to content development starts with knowing what genes to include, and which to exclude through a proprietary pruning process, and also includes curating single-cell data based on feedback from key opinion leaders. The company will often share a draft of the genes it wants to feature in a panel under a nondisclosure agreement before locking in a final list, Piazza said.
“If you select the wrong dataset, you make the wrong choices. So we’re very cautious about ensuring that the single cell datasets that we did make decisions based on were as broad as the application areas we wanted to cover,” Piazza explained. “You want to look at normal tissues, disease tissues. What those genes are doing in those contexts informs the decisions you make while you prune. So, there’s a heavy lift of a panel. But we’re really, really pleased with how it turned out.”
NanoString will not disclose the list price for CosMx Human 6K or other products, citing numerous variables. Human 6K is designed for use with NanoString’s CosMx™ Spatial Molecular Imager (SMI), which offers single-cell RNA and protein imaging with what the company says is the most precise cell segmentation and highest plex available. CosMx SMI also delivers cell typing and spatial context, and accurately measures the transcriptional programs within cells that result in disease or health, according to NanoString.
Piazza said her company’s 6,000-plex panel will someday give way to an even larger panel. During AGBT, NanoString demonstrated what it said was true single-cell whole transcriptome analysis capabilities, releasing the first such public data set.
NanoString expects to make a whole transcriptome panel product commercially available in 2025.
“We’re calling the 6K panel high plex today, but hopefully tomorrow it will be the mid-high plex, as we’ve started already talking about our CosMx whole transcriptome panel,” Piazza said.
