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AGBT: NanoString, 10x Genomics Plan High-Resolution Spatial Assays to Detect Thousands of RNAs

NEW YORK – NanoString Technologies and 10x Genomics each announced plans last week to release single-cell resolution spatial genomics assays that can detect thousands of transcripts at once.

The companies shared their plans at last week's Advances in Genome Biology and Technology annual meeting.

In a conference talk, NanoString Chief Technology Officer Joe Beechem described the firm's plans to launch panels for the CosMx instrument to detect 6,000 RNAs, up from about 1,000. The panels, slated for launch in the first half of 2024, will also be able to profile up to eight proteins on the same slide. A separate protein-only assay will nearly double the number of proteins detected to 119, from 64.

"You're not really going to miss any major biological activity that happens in a tissue," with this new assay, Beechem said. "We're not trying to match a cell typer. We want to build an imager that understands all the biology." 

The 6,000-RNA panel also unlocks the ability to impute data from whole-transcriptome technologies such as lower-resolution spatial methods or single-cell RNA sequencing, he said.

In a company-sponsored workshop, Malte Kühnemund, 10x Genomics' director of R&D for in situ technologies, shared proof-of-concept data from a panel for use with the Xenium platform that can detect 5,000 RNAs. At present, Xenium panels can profile hundreds of RNAs. The firm has demonstrated the use of the new panel in 700,000 cells across seven different human tissue types — brain, lung, skin, colon, pancreas, liver, and kidney — including formalin-fixed, paraffin-embedded samples.

10x did not provide information on how the highly multiplexed assay will be integrated into future products or when it might be available.

In a note to investors last week, Cowen Analyst Dan Brennan called the expanded spatial gene expression assays "notable." NanoString's announcement was "arguably … the most standout news of the conference," he wrote.

The increase in RNA analysis capabilities at high resolution suggests that NanoString's and 10x's platforms may offer some use for discovery and not simply targeted analyses. At times, companies have suggested that whole-transcriptome approaches would be used to discover interesting gene expression patterns and that these more focused platforms would zero in on previously identified molecules.

Earlier in the week, Weill Cornell Medicine's Chris Mason described his lab's efforts to create a spatial atlas of human tissues using NanoString's CosMx and GeoMx platforms, which he suggested could enable ligand-receptor analyses, as well as the study of ribosomal and other organelle biology and of cytoskeleton shifts.

Indeed, Beechem showed data demonstrating the ability to find "hotspots" of co-expressed ligands across different cell types using the 6,000-plex assay.

"To fully map the sub-cellular functions and cellular interactions with spatial technology, the greater throughput is needed, especially as we discover and annotate rare and dynamic cell states," Mason told GenomeWeb. "There are over 62,000 genes annotated by GENCODE, so we're still just getting started on the full cellular map of RNA functions — getting to 6,000[-plex] gets us 600 percent further."

These high-plex assays from 10x and NanoString may not even be close to the ceiling of what's possible with high-resolution spatial profiling. Beechem's presentation, for example, hinted that NanoString is working on a whole-transcriptome CosMx assay.