MARCO ISLAND, Florida – Targeted transcriptomics, a new capability teased last week by 10x Genomics, will be available by the end of 2020, the company announced at the Advances in Genome Biology and Technology meeting held here this week.
With four panels covering more than 1,000 genes each, the product can get the same results for its targets as whole transcriptome profiling, with just a fifth of the number of reads per cell, 10x Staff Scientist Sarah Taylor told attendees of a lunchtime workshop sponsored by the single-cell, and now spatial, analysis company.
Taylor and other company representatives described three other new products the company plans to launch in 2020, aside from targeted gene expression library preparation kits: CellPlex kits to increase the scale of experiments, the Chromium Single-Cell ATAC + Gene Expression kit, and immunohistochemistry compatibility for the Visium spatial genomics platform.
The company also announced a new Visium certified service provider program, improvements to its Cell Ranger software, and plans to bring its analysis software suite to the cloud by the end of the year.
More new products and capabilities for Visium — including feature barcoding and a 10x-developed solution to make it compatible with formalin-fixed paraffin-embedded (FFPE) samples — are slated for the first half of 2021.
Revealed on a conference call with investors last week, the new products, "will empower scientists to study biology at greater resolution and scale than ever before," Michael Schnall-Levin, senior VP of R&D, said in a statement.
Following an update on peer-reviewed publications made possible with the firm's technology, Taylor took the stage to speak about products for Chromium.
The initial foray into targeted transcriptomics will comprise four hybrid capture-based kits. The Pan-Cancer panel will target about 1,250 genes; Immunology, about 1,050 genes; Human Gene Signature, about 1,140 genes; and Neuroscience, about 1,150 genes. The company also plans to offer customizable and even completely custom panels at a later, unspecified date.
The kits work by capturing transcripts generated from 10x's 3' and 5' gene expression libraries using streptavidin beads. They tile across the entire transcriptome, including transcription start sites, untranslated regions, and coding regions and allow detection of gene isoforms. The products will also be compatible with feature barcoding.
Taylor shared data from internal experiments showing the targeted panels were well correlated with results from 10x's whole-transcriptome profiling and also preserved cell clustering, while using up to 80 percent fewer reads per cell, from about 20,000 reads per cell down to about 4,000.
Customers will also be able to sign up for an online design tool where they can add up to 200 customizable genes to each panel, or design completely custom panels.
While some customers have come up with their own ways to multiplex single-cell sequencing experiments, such as cell hashing and antibody-based approaches, 10x has now developed its own multiplexing method.
Using oligo-conjugated lipids that integrate into the cell wall, CellPlex reagents will allow researchers to either combine samples or subdivide a sample and run it on a single Chromium lane.
"Now we're supporting 20,000 single cells recovered per channel," Taylor said, a three- to four-fold increase.
The product will launch with 12 multiplexing oligos, which can be demultiplexed with updated Cell Ranger software and linked to whatever libraries were generated from that sample. The method is species and cell-type agnostic, Taylor said.
Taylor added that 10x will be extending Visium's dual-indexing capability across all its product lines and Cell Ranger will be four times faster, while also supporting all the new capabilities.
ATAC-Seq + Gene Expression
Next, Staff Scientist Kamila Belhocine discussed 10x's combination of the assay for transposase-accessible chromatin by sequencing (ATAC-seq) plus gene expression for single cells.
"This is the product we have been after for the last two years, since we introduced ATAC-seq," she said. Having both datasets will "establish a true linkage" to help "build regulatory networks and understand how they're influencing gene expression," she said.
Belhocine displayed internal data showing the saturation curve for the combined assay, compared with the single-cell gene expression assay. "As you sequence, you're still extracting valuable information," she said. And it compares well with the gene expression kit, she said.
"We're bringing you this assay with no compromise on the sensitivity," she said.
She also demonstrated how, in analysis, one could move from gene expression-based cell clustering, into so-called "ATAC-space" and back, showing slight differentiation that wasn't obvious at first. "You can toggle between the two spaces," she said, which can help establish links between cell state-specific features.
Targeted gene expression is also available on Visium, but that isn't the only upgrade coming to the nascent platform, Nikhil Rao, 10x director of strategic and product marketing, told the workshop crowd.
In addition to IHC compatibility, 10x is working on bringing feature barcoding and immunofluorescence to Visium.
10x is also taking a "two-pronged" approach to making Visium work with FFPE samples. It's working with several early-access partners on a modified protocol of its extant product, including researchers at Sweden's Science for Life laboratory, led by Joakim Lundeberg (a coinventor of spatial transcriptomics technology acquired by 10x and the basis for Visium). It's unclear where this modified protocol came from, but presumably it wasn't from 10x, because Rao said the company is developing its own solution form making Visium work with FFPE samples, which it plans to release in the first half of next year.
Rao also said 10x is establishing a certified service provider network for Visium. The Icahn School of medicine at Mount Sinai, Stanford University, and the UK's Newcastle University are the first three partners, but 10x hopes to have seven more by mid-year.
Moreover, 10x is establishing a Clinical Translational Research Network with the goal of "enhancing clinical translational research workflows with Visium," a spokesperson said in an email. "Benefits of joining the network include special pricing and access to a host of exclusive services, including the ability to present at a 10x summit in the future." Initial members include the Lieber Institute for Brain Development at Johns Hopkins University and France's Centre de Recherche des Cordeliers and Centre de Recherche en Cancérologie de Lyon.
10x Genomics Cloud
Last, 10x senior VP of software and infrastructure Alex Wong talked about the company's push to make Cell Ranger, Space Ranger, and Loupe analysis tools available in the cloud.
"That means no stressing about hardware," he said. "You no longer need to compete with other users at your institution" for computing resources.
Perhaps even better: a "standard amount of analysis" will be included with each reagent kit purchase, he said. After the workshop, Wong told GenomeWeb that "the intent is to make life as easy as possible for our customers and to speed up their ability to do larger experiments and make it as affordable as possible."