Spatial Surge: AGBT Updates On Single-Cell and Spatial Genomics, In Situ Analysis, More

By Allison Proffitt

March 4, 2021 | A host of sponsors and vendor companies attended the virtual AGBT General Meeting this week. Through sponsored talks and even more poster sessions, vendor companies shared their latest work and technology developments and made product announcements.

“It is through genomics that we finally appear to be taking back control from the COVID pandemic and starting to bring some normal into our lives,” Terry Lo, CEO of Vizgen said in his presentation. And that optimism was evident in the progress and new products on display from the technology community.

Vizgen’s Integrated Single-Cell, Spatial Genomics System

Vizgen CEO Lo announced his company’s MERSCOPE platform, which combines single-cell and spatial genomics analysis in one integrated system, providing a streamlined workflow from sample preparation through data visualization for broad applications in both fundamental biology and medicine. Lo called the MERSCOPE platform, “the first high multi-plexing, high resolution in situ commercial platform that not only provides spatial context across entire tissues sections, but also provides the most sensitive gene expression profiling for single cells.”

MERSCOPE is based on the MERFISH technology, multiplexed error robust fluorescence in situ hybridization, developed in the laboratory of Dr. Xiaowei Zhuang, a Howard Hughes Medical Institute Investigator, and David B. Arnold, Jr. Professor of Science at Harvard University. Vizgen was created to license the technology in 2019.

Vizgen’s MERSCOPE offers combinatorial labeling, sequential imaging, and error-robust barcoding, providing the highest detection efficiency available for spatially profiling gene expression across whole tissues and resolving individual transcripts with nanometer-scale resolution, according to the company. Hundreds of genes can be profiled within hundreds of thousands of cells in a single instrument run without the need or cost of sequencing. The Vizgen visualization software processes all the imaging into simple-to-use output and data imaging files, Lo said. These files can be viewed with Vizgen tools or analyzed with other tools that users would use with single-cell sequencing data.

Lo said MERSCOPE will be available for commercial release in the summer of 2021.

NanoString’s Whole Transcriptome Atlas and Spatial Molecular Imager

Joseph Beechem, CSO and senior vice president of research and development at NanoString Technologies shared his company’s latest launch: Whole Transcriptome Atlas (WTA) for human tissue using the NanoString GeoMx Digital Spatial Profiler (DSP). (WTA for mouse is coming in Q2.) The WTA provides an unbiased, spatial view of all protein-coding genes and is designed for NGS readout on Illumina sequencers. It extends the GeoMx RNA assay portfolio from a focus on oncology and immunology to new applications in neuroscience, developmental biology, and additional diverse fields.

While GeoMx DSP is designed for spatial biology at the multi-cellular level, Beechem also highlighted the Spatial Molecular Imager platform, which was announced in December and is designed for spatial biology at the single cell and sub-cellular level. SMI develops NanoString’s Hyb and Seq chemistry that began development in 2016, Beechem said, but instead of ordered array sequencing, the SMI platform now brings the Hyb and Seq chemistry into in situ tissues. The Spatial Molecular Imager returns exact spatial coordinates—x, y, and z axes—for every multiplexed RNA in every cell, Beechem said. NanoString is opening an early technology access program for the SMI platform.

“This is really a revolution in what can be done on these normal FFPE samples,” he argued. “This brings our two platforms together: the Spatial Molecular Imager… operates on this 10 micron and above sub-cellular resolution on these key transcripts all with single-cell sensitivity. And our GeoMx high-plex digital spatial profiler looking at these unique geometries at the whole transcriptome level. Together they represent a real revolution in what you can do to discovery new effects in spatial biology.”

PacBio Applies HiFi to SARS-CoV-2 and Rare Diseases

Jonas Korlach, CSO at PacBio, gave updates on PacBio’s work—focusing specifically on HiFi reads and their applications in SARS-CoV-2 research and undiagnosed diseases. PacBio’s HiFi reads are the preferred sequencing approach for tracking SARS-CoV-2 mutations, Korlach argued, because only 4.5% of the genome is covered by primer sequencing, leaving the vast majority exposed for sequencing to reveal variants. Longer, 99.9% accurate HiFi reads also detect more variant types including SNPs and indels, he continued.

In fact, Korlach positioned PacBio as the best sequencing platform for pathogen surveillance in the future as well based on the read length and cost. “While today’s efforts and focus are on detecting COVID-19 in our communities, the infrastructure that is being developed will bode well for our preparedness and sophistication for fighting COVID-19 and other pathogens in the future,” he said.

Korlach also spent some time on PacBio’s utility for rare and mendelian diseases. PacBio offers a more complete detection of SNVs, indels, CNVs, phasing, translocations, inversions and repeat expansions, he said. “With more complete detection of all of these variant types, we can anticipate a great explanation rate.” In fact, citing a list of previously-unexplained genetic disorders with resolutions thanks to HiFi sequencing, Korlach posits that more than half to two-thirds of unexplained genetic disorders could be explained with PacBio sequencing today, and he expects that number to rise as analytical tools improve. He highlighted an open source analytics workflow for PacBio reads available on GitHub that will soon be available on Microsoft Azure.

Korlach also mentioned a goal set out by both PacBio and Invitae earlier this year at the JP Morgan Healthcare conference when announcing their collaboration: the goal of the genome as a platform. “This concept of having the genome as a platform and mining this platform for information that may be needed during the different stages of a person’s life and applying it for different types of disease areas is a powerful paradigm for precision medicine,” he said. PacBio intends to continue to improve all aspects of sequencing to realize this vision, Korlach said, making the genome as a platform ever more efficient and cost-effective in the future.

New Name for OnRamp Bio, Single-Cell Web-Based Analysis

OnRamp Bio unveiled its new corporate identity at AGBT, taking the name of its cloud-based SaaS ecosystem, ROSALIND. ROSALIND, “enables the last mile of discovery and collaboration” in multi-omic data analysis, said CEO Tim Wesselman, analyzing and interpreting RNA-seq, miRNA-seq, ChIP-seq, ATAC-seq, NanoString, and now single-cell RNA-seq data.

The company’s new solution for single cell data analysis adds web-based collaboration and the analysis and interpretation of 10X Genomics-generated single cell data to the company’s other data types. Wesselman called it “a vivid user experience” that will allow global collaboration on single-cell data from FASTQ files to cell identification to pathway exploration. But Wesselman was particularly excited about single-cell cluster annotation. “This is where it all comes together in one complete, end-to-end solution.”

10x Updates, On Track For New Chromium, Visium, In Situ Platforms

Sarah Taylor, applications team lead at 10x Genomics, gave highlights of the Chromium Single Cell platform, the Visium Spatial Genomics platform, and the upcoming in situ platform building on the Readcoor and Cartana acquisitions.

Building on announcements made at the JP Morgan Healthcare Conference in January, Taylor touched on the Chromium X and high throughput kits and fixed RNA profiling, both expected in the second half of 2021. She also introduced high throughput antibody discovery on the Chromium platform—barcode enabled antigen mapping, BEAM. BEAM will enable users “to isolate highly-specific antibodies against multiple antigens across different species in a single experiment,” Taylor said. The software solution delivers antigen-specific antibody isolation from blood or lymph nodes in days. Users should expect BEAM in the first half of 2022, she said.

For the Visium Spatial Genomics platform, Taylor reiterated delivery dates of CytAssist, the new instrument for the enablement of pathology-driven workflows, and Visium HD, the highest-resolution spatial platform yet, in the first half of 2022. Visium for FFPE is on track for delivery in the next few months, she said.

The forthcoming In Situ analysis platform is “geared toward researchers who know what they are looking for and want to focus on specific targets at single-molecule resolution,” Taylor said. The solution will be integrated with hardware, software, and reagents and, “will enable high-plex multi-omics to interrogate transcriptomics and proteomic analytes simultaneously.”

Rebus Biosystems’ Spatial Omics Platform

Rebus Biosystems launched the Rebus Esper spatial omics platform, leveraging Rebus Biosystems’s patented Synthetic Aperture Optics (SAO) technology, a super-resolution technique that allows routine quantitative analysis of tens of millions of cellular features across hundreds of thousands of cells. In November, Rebus closed a $20 million Series B financing round, led by Illumina Ventures.

The first assay to be released for the Rebus Esper platform is the Esper High Fidelity assay. This ultra-sensitive assay, based on cyclic single-molecule fluorescent in situ hybridization (smFISH) chemistry, can resolve and map individual RNA molecules in their original locations, giving researchers a complete picture of tissues across a wide range of expression levels for up to thirty custom genes. During 2021, the Esper High Fidelity suite of assays will enable higher level of multiplexing and protein co-detection. In addition, the company will focus on developing assays enabling multiplex gene expression in formalin-fixed, paraffin embedded (FFPE) samples and simultaneous analysis of over 1000 genes.