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10X Genomics Moves out of Shadows with Planned Launch of Synthetic Long-read Technology in 2015


NEW YORK (GenomeWeb) – Operating in stealth mode since its founding about three years ago, 10X Genomics emerged last week with a bang, announcing it raised $55.5 million in a Series B financing round and plans this year to commercialize a technology that it said could "change the definition of sequencing."

Speaking to GenomeWeb on the sidelines of the 33rd Annual JP Morgan Healthcare Conference a week ago, officials from 10X outlined its technology, which the company will present in greater detail at next month's Advances in Genome Biology and Technology conference. Used in conjunction with existing next-generation sequencing instruments, the company's technology would allow researchers to generate information about the human genome that currently escapes elucidation, 10X CEO and Co-founder Serge Saxonov said. 

While current sequencing technology can generate huge amounts of data, it does so in a fragmented fashion, Saxonov said, resulting in a loss of information about structural variations and haplotyping, for example. Additionally, elucidating certain regions of the genome, such as the HLA and SNPs in pharmacogenetic genes, remains a challenge even though they are critical to understanding diseases and drug treatments. 

"That's the problem we are trying to solve," Saxonov said. 10X's technology, "indexes the genome, allowing you to preserve valuable and otherwise lost information, such as haplotype phasing and structural variants derived from whole-genome, exome, and targeted approaches," and "economically uses output from current short-read NGS platforms," he added. 

While the NGS market is poised to explode — by some estimates, it could approach $9 billion by 2020 — Saxonov said "the technology needs to improve significantly in order to get to this point." If sequencing is to fulfill its potential, especially in the clinical space, "we need to be able to read the genome in a more comprehensive fashion. From that perspective, the market opportunity [for 10X] is tremendous," he said. 

10X's approach is a synthetic long-read technology that leverages existing short-read NGS technology but fills in knowledge gaps through a combination of microfluidics, chemistries, and informatics. According to Saxonov, 10X takes a sample of DNA and partitions the molecules in a massively parallel manner. Each partition has its own barcode, and once the partitioning is completed, the fragments are then pieced together into a long read. 

Within the fragments, the embedded barcodes that provide information about the particular group of reads come from the same partition, meaning they come from the same molecules, Saxonov noted. 

With current standard workflows, a researcher who wants to partition a molecule can do perhaps 300 partitions or a few hundred barcodes, he said, but for sequencing, hundreds of thousands of partitions are needed, and to get to that level a new approach using multiple disciplines was required. 

10X was founded in 2012 drawing on the know-how of Saxonov, whose background is in biomedical informatics; Kevin Ness, whose expertise is in microfluidics; and Ben Hindson, whose training is in chemistry. 

All three had been with digital PCR firm QuantaLife through its acquisition by Bio-Rad Laboratories in late 2011. In addition to being 10X's co-founders, Ness is the company's CTO and Hindson serves as its CSO. 

After the three left Bio-Rad, they decided to regroup to create what they saw as a "big opportunity, a big value in the sequencing world," Saxonov said. They raised $4.5 million in seed financing and spent the early days of 10X's history deciding on a correct platform and "how [to] actually make it work," Saxonov said. "It's a big challenge to convert one reaction to hundreds of thousands of parallel reactions." 

Those challenges included increasing the scale to the point where it would be useful, delivering "the huge diversity" of barcodes, and improving the biochemistry so that DNA wouldn't be lost during the labeling and sample preparation steps. 

Saxonov also noted that a lot of work has gone into the bioinformatics end of the technology. "And the informatics, the computational biology is what is driving the overall specs and the overall direction of the different parts of the product," he said. 

After generating proof-of-concept data, 10X, which is based in Pleasanton, Calif., raised $20 million in a Series A financing round last year led by venture capital firm Venrock. 

Rob Tarbox, vice president of marketing for 10X, told GenomeWeb that the firm's technology has been developed to fit seamlessly into researchers' current sequencing workflows. 

"Most of the processing is largely synonymous up front with how people work with nucleic acids today as they go into next-gen sequencing," he said. "And then similarly on the back end … there's a small perturbation in the downstream software to allow customers to extract that information but live largely within the confines of the software packages and tools that they are leveraging today." 

Saxonov said that the software is open and modular so that researchers would be able to integrate it with their existing packages and programs. Additionally, 10X will offer tools to help researchers develop custom applications to leverage the firm's molecular barcoding approach. 

10X's platform, the name of which will be unveiled at AGBT, is currently configured for use on Illumina's fleet of next-generation sequencing platforms, though there is no formal relationship between the two companies, Saxonov said. 

Indeed, when the platform becomes commercially available, it would compete with Illumina's TruSeq Synthetic Long Reads technology, which Illumina acquired in its purchase of Moleculo two years ago.

Saxonov, however, noted that 10X's platform, which will launch with a price tag of $75,000, is different from Illumina's system in several ways. The 10X instrument is designed "to encompass a wide range of applications and use cases, including cancer genomics, which requires both a high number of unique partitions and barcodes," Saxonov said, adding the scale of 10X's instrument is about 1,000 times greater than Illumina's.

Also, 10X's biochemistry allows the system to use DNA from standard extraction kits, where the size range can fall between 10 kb and more than 100kb, and still use about 1 ng of input, or about 500 times less than what Illumina's technology requires, Saxonov claimed. 

"Our product automates the partitioning and molecular barcoding steps that are onerous [with TruSeq Synthetic Long Reads technology] and similar approaches, while leveraging simple workflows and protocols that are commonplace in NGS today," he said. "The instrument generates the equivalent of 1.6 million pipette steps in about five minutes from a single-button operation." 

He declined to provide specifics about 10X's commercialization plans for its technology, saying only that part of the $55.5 million Series B financing will be used for those efforts, as well as continued development of the technology, which will be initially targeted to the research-use-only space. 

Eventually, it will be made available to the clinical market as well, though there are no plans at the moment to seek US Food and Drug Administration approval for the technology, Tarbox said. 

During AGBT, the company will present data for its technology generated by its collaborators, Saxonov said, though he declined to identify them.