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Genomics Researchers Embrace Proteins at AGBT


NEW YORK — "Protein" is no longer a dirty word at AGBT. While the traditional focus of the annual meeting, which took place in Hollywood, Florida, last week, is right there in its name — Advances in Genome Biology and Technology — protein biology and technology have now found their place at the conference.

"I've been surprised at how protein-friendly the AGBT crowd has gotten," said Niro Ramachandran, chief business officer at Akoya Biosciences. "Fifteen years ago, 'protein' would be like a swear word here."

Akoya is one of several companies whose technology offerings lean heavily on protein analysis, although it has instruments that can also detect RNA. At this year's meeting, several companies made splashes talking about their protein detection technologies, in particular in the context of spatial omics analyses. Of course, it helps to be detecting proteins with DNA barcodes.

Pixelgen Technologies, a Swedish startup, for example, stepped out in public to share its NGS-based technology for spatial resolution of cell surface proteins. Its compatriot Olink, a publicly traded company pursuing NGS-based detection of proteins, shared data from large cohort studies.

And bigger companies, especially those advancing spatial omics, like 10x Genomics, NanoString Technologies, and Akoya, as well as their customers, also spoke about proteins. "The protein information, although modest, gave really important information on cell structure," said Mark Adams, a professor at the Jackson Laboratory, commenting on a presentation by Weill Cornell Medicine's Chris Mason on the use of NanoString's platforms to create human tissues atlases. Spatial technologies will show "what people have known forever … which is that RNA levels don't correlate with protein levels," he added.

Ramachandran credited single-cell RNA-seq for paving the way to a protein-friendly AGBT.

Serge Saxonov, CEO and cofounder of 10x Genomics, agreed that his company's single-cell assays, which can pair antibody panels with transcriptomics, made proteins analysis more palatable to the AGBT crowd. "There had been pent-up interest to move in that direction, and people have been expanding that direction," he said.

At the conference, 10x presented a poster demonstrating a marriage of its sample multiplexing capabilities with cell surface protein detection in single cells. Previously, the barcoding schemes used in these were not compatible, but 10x has now demonstrated that it can multiplex samples using TotalSeq-C antibody libraries in fixed cells from BioLegend.

10x also said that it will offer a multiomics kit for its Visium spatial platform that can detect protein and gene expression on the same formalin-fixed, paraffin-embedded tissue section, as well as a 35-plex human immune cell profiling panel for the Visium CytAssist instrument. Both products are expected in the first half of 2023.

NanoString is also planning to add co-detection of RNA and protein to its new high-plex CosMx spatial molecular imager gene expression assays, as well as to increase the number of proteins in protein-only panels.

Olink's Cindy Lawley, meanwhile, presented data from target and biomarker discovery studies in large cohorts. In a study of UK Biobank samples, the firm discovered more than 10,000 protein quantitative trait loci — associations between genetic variants and plasma protein levels — 85 percent of which were novel, she said. Also, a study of 3,019 subjects as part of the SCALLOP (Systematic and Combined AnaLysis of Olink Proteins) consortium yielded 44 proteins associated with heart failure.

Pixelgen, fresh off a $6 million seed funding round announced in December, presented a poster on its so-called "molecular pixelation" technology. The firm uses oligo-tagged antibodies to lock onto proteins, a ligation reaction to connect nearby barcodes, and NGS as a readout.

"It's a new approach to visualizing proteins without microscopes," Senior Marketing Manager AnnaLotta Schiller said. Not only can the technology count proteins, but it also can provide information on their spatial arrangement on the cell. It can tell, for example, if the proteins are dispersed, clustered, or even concentrated at one "pole," such as in some cell binding events.

The firm's kits offer the ability to analyze 75 proteins in up to 1,000 cells, with eight reactions in a kit. The method requires about 100,000 sequence reads per cell, Pixelgen CEO and Cofounder Simon Fredriksson said.

As the proteomics and next-gen sequencing worlds nestle ever closer to each other, it begs the question of how long it will be until protein sequencing firms start showing up at AGBT. 

"Mass spec is great, but of course it can't really work at the single-molecule level," JAX's Adams noted, so interest in protein sequencing is out there. He heads a new grant coordinating center for sequencing technology development and education at JAX, funded by the National Human Genome Research Institute, which includes protein nanopore sequencing grants.

Overall, the meeting showed that technology shifts can happen in just a few years. "Five years ago, with Olink, nobody was listening," said Pixelgen's Fredriksson, who also cofounded Olink. "They're listening today."