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Parse Biosciences Lowers Cost Barriers to Single-Cell Transcriptomics Research

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This story has been updated to reflect additional pricing information from 10x Genomics. 

NEW YORK – Parse Biosciences, a single-cell genomics company commercializing the split-pool ligation-based transcriptome sequencing method (SPLiT-seq), has a pointed message for the rest of the market.

"For too long, labs have been held back by technologies that not only compromise on data quality, but which also don't scale to match researchers' ambitions," Parse CEO and Cofounder Alex Rosenberg said in a statement last month announcing the commercial launch of the firm's single-cell whole-transcriptome kit.

The University of Washington spinout, which was founded as Split Biosciences and changed its name earlier this year as part of a $7 million Series A financing round, is quick to point out that its method does not rely on microfluidics and therefore does not require a separate instrument, a fact that seems to be aimed especially at 10x Genomics, whose Chromium controllers alone can cost $75,000. Bio-Rad Laboratories' ddSeq single-cell solution also requires its own machine.

Even for those with the budget to run samples on Chromium, Parse offers a raft of features that existing plate- and droplet-based single-cell library preparation methods can't match at the moment. The Parse kit can process up to 100,000 cells in total from up to 48 samples at a time. Also, because the cells are fixed as part of the sample prep, they can be collected as they're available and stored, for as long as six months, until there are enough cells to run the whole kit.

And for those who have been wary of the sticker price for 10x's Chromium single-cell gene expression reagents — which start at approximately $6,000 for four reactions and run more than $20,000 for 16 reactions, Parse's combinatorial barcoding-based scheme has a retail price of $8,800 per kit, according to one user.

10x's single-cell gene expression solution captures up to 10,000 cells per sample. At eight samples per microfluidic chip, it can process up to 80,000 cells at a time, for about $11,000 in total reagent costs, a 10x spokesperson said in an email. For comparison, Bio-Rad's kits cost about $2,000, according to a user, processing up to four samples with advertised throughput of 9,600 cells per sample but an observed throughput two or three times that, the user said.

Both Parse and 10x preferred to frame costs on a per-sample basis. "Customers can expect [costs of] approximately $200 per sample, or $.09 per cell," Parse said, while 10x said costs are "roughly" $1,400 per sample for a full eight-channel Chromium chip. However, many core labs offer 10x single-cell transcriptomics at a cost of $2,000 per sample, or more.

These features will not be a differentiator for Parse for long, though. 10x's CellPlex technology, released earlier this month, will allow multiplexing up to 12 sample in a channel and could lower costs to the range of $200 to $700 per sample, depending on the number of samples, the company said. And 10x has been vocal about plans to offer the ability to process fixed cells and to provide even higher throughput — as many as 1 million cells at a time on the new Chromium X — both of which should be available by the end of the year.

The Parse team, however, seems confident in its ability to take this opening and snowball any advantage. "To a degree, everyone is realizing there's a need for more scalable solutions," Rosenberg said. "But the simplicity of our approach is going to allow us to keep pushing the envelope faster than anyone else."

So far, Parse is off to a decent start. All of the 50 early-access program participants have placed orders with the company, Rosenberg said, though he declined to provide more information. One early-access customer has already ditched Bio-Rad's ddSeq method for Parse, he said, in all applications except a single-cell assay for transposase-accessible chromatin by sequencing (ATAC-seq). Users touted the product's low cost, easy of use, good sequencing results, and efficiency as positives.

The kit has also piqued the interest of core labs. "This is very appealing as we rarely have enough budget for new and fancy equipment," said Luciano Martelotto, scientific director of Harvard Medical School's single-cell core lab. While he has not yet used the Parse technology himself, he is planning to, soon. "I'm super keen," he said, "I really look forward to getting my hands on it and seeing what magic we can do."

Rosenberg said Parse plans to use its recent Series A financing for the commercial rollout and for further R&D. The company had 18 employees as of last month and is "still growing fast," he said.

SPLiT-seq offers the ability to analyze fixed cells without specialized equipment, but Parse has done additional development.

"One of the shortcomings at the time was definitely sensitivity, with respect to genes detected per cell," Rosenberg said. "That's really important for how much resolution you have in your data and what types of cell types you find." Moreover, it could reduce the total cost of the experiment.

"In large part, focusing on improved sensitivity means you're going to be able to detect larger numbers of transcripts or genes on the same level of sequencing," Rosenberg said. He touted a doublet rate of 3.4 percent per 100,000 cells, whereas 10x publicizes a doublet rate of 3.9 percent per 5,000 cells, though doublet rates can grow with .

At the median, Parse's kit offers detection of about 12,000 genes per cell in studies with HEK 293 cell lines, up from 5,000 with SPLiT-seq, and compared to a median of about 5,000 genes for 10x's Chromium single-cell gene expression kit v2, according to a benchmarking study from researchers at the Broad Institute, first posted to BioRxiv in 2019 and published last year in Nature Biotechnology.

The Parse kit also captures 100,000 unique molecular identifiers per cell, essentially the number of transcripts, up from 20,000 UMIs per cell with SPLiT-seq.

Parse's kit is highly efficient, according to Liz Rebboah, a graduate student at the University of California, Irvine, who used it as part of the early-access program. She was able to get data from approximately 95,000 cells or nuclei per kit by loading 1 million cells taken from mouse brain tissue. "When I was doing cell lines, I was closer to 100 percent [efficiency]," she said. 

The company has also worked on streamlining the workflow, aiming to make it as easy as possible. Their efforts seem to have paid off. "Everything was so straightforward," said Larry Reiter, a researcher at the University of Tennessee Health Science Center who studies the genetics of neurological disease and is an early-access customer of Parse. "It's a basic idea, but it was really well done on their part." 

The option to work with fixed cells "is just wonderful," Rebboah said. "The hardest part of any single-cell experiment is preparing the sample," a process that can take six to eight hours. "With Bio-Rad, you have to go right into library prep, so it's not a fun day. You're exhausted by the end of it," she said. Rebboah said she had only run as many as seven samples at once and had not yet tried to max out the limit of 48.

Martelotto suggested that the ability to fix cells and run them all at once will help scientists doing prospective clinical trials. Rosenberg added that the multiplexing capabilities provide additional appeal to pharmaceutical companies that are interested in running thousands of samples in a clinical trial.

The early-access researchers also said they learned important aspects of the kits during the program. "We found we got better overall data out of the 3,000-cell setting than the 500-cell setting," Reiter said. "I would have loved to know we could do it at 3,000 cells right away, but that's just not how life goes. You'll have a cell line and you have to assess depth of coverage, you can't just guess that off the top of your head."

Rebboah noted that the company was responsive to any issues and even processed data for her. Additionally, she was "impressed" by their software analysis package. "This kind of analysis pipeline should be standard," she said.

Parse said orders have so far exceeded expectations, but declined to provide specifics on early sales for the kit and was cagey about its schedule for new product features going forward. The company is looking to push the throughput even further, Rosenberg said, and automation "is definitely something we've heard customers are interested in. I can say we've listened to that, for sure." Immunology is an application area that the company plans to address in the future, he added, and he mentioned multi-omics as another feature researchers should expect to hear more about.

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