NEW YORK (GenomeWeb) – In 2015 next-generation sequencing went long. Sequencing prices fell, technology improved, and researchers can now get long-read lengths and are starting to evaluate long-range genomic information using NGS and supporting technology.
According to a recent market report by DeciBio, the market for NGS manufacturers hit $2.4 billion and is expected to grow to $4.5 billion by 2019. Clinical customers will primarily drive this growth, while the research market will be driven by single-cell sequencing, population genomics, and novel NGS applications.
Pacific Biosciences' launch of the Sequel instrument, the numerous publications by users of Oxford Nanopore Technologies' MinIon instrument demonstrating that the technology works and is rapidly improving, and the promise of 10X Genomics' technology excited experts in the field the most in 2015.
In addition, although Illumina continues to be the dominant player in the market, the firm missed its revenue guidance in the third quarter due to selling fewer of its MiSeq and NextSeq instruments than it expected.
Keith Robison, principal scientist at Warp Drive Bio and author of the Omics! Omics! blog, said that Illumina was "coasting" this year, although he and others speculated that the company might have a significant announcement in 2016, such as patterned flow cells for all its instruments, a remake of the MiSeq, and a nanopore sequencing device, among the potential innovations suggested by Robison and others.
Meanwhile, BGI initially looked like it had commercialized Complete Genomics' technology with the launch of Revolocity, which was expected to compete with Illumina's HiSeq X Ten, but then pulled an about-face several months later, shelving the system and saying it would focus on its desktop instrument.
Thermo Fisher Scientific launched a new NGS system based on the Ion Torrent technology, the Ion S5, which will focus on "plug-and-play" targeted sequencing. The firm has also continued to develop targeted panels based on its AmpliSeq technology, particularly in the cancer space. Going forward, targeted sequencing will likely be its niche, as it has struggled to meet its goals of scaling up its Proton instrument.
In its report DeciBio said that it believes Thermo Fisher has lost market share due to "continued technical difficulties with the PII chip," but as the company shifts focus from increasing throughput to improving workflow for clinical customers, it will grow in line with the market, at about 17 percent per year, Stephane Budel, a partner at DeciBio said.
Overall, "Illumina will remain dominant," he said, "but there will be more noise from other competitors capturing a number of little niches."
Don't call it a comeback
Over the last few years, Pacific Biosciences has been steadily improving its RSII instrument — each year substantially increasing read lengths, throughput, bioinformatics, and applications. Yet, the instrument's hefty list price at $695,000 and footprint has hindered broad adoption in the community.
But, the launch of Sequel — which boosted throughput seven-fold while reducing the cost to $350,000 and the footprint to about one-third that of the RS II — could signal "the comeback of PacBio," Jay Shendure, a professor of genome sciences at the University of Washington, told GenomeWeb.
PacBio expects to ship 10 instruments in 2015, the majority of them to Roche, which will use the Sequel to form the basis of a clinical sequencing instrument that it is developing. The Icahn Institute for Genomics and Multiscale Biology at Mount Sinai's Icahn School of Medicine and Baylor College of Medicine have also placed orders for Sequel instruments.
If the Sequel "continues to steadily improve, it would be pretty remarkable to get low-cost genomes with the long-read lengths to support more comprehensive variant detection," Shendure said. The instrument even offers the possibility of generating "platinum quality genomes," which he defined as approaching the quality of the human reference genome.
James Hadfield, head of genomics at Cancer Research UK, who blogs at CoreGenomics, told GenomeWeb that PacBio could be a real competitor if it can continue to improve on its loading efficiency and push its sequencing costs down. "It might be that we get to the $5,000 genome on PacBio, and that would be really great," because although it would still be more expensive than sequencing a genome on an Illumina machine, it could provide additional long-range and structural information, he said.
Mick Watson, director of ARK-Genomics at the Roslin Institute, predicted that in the coming year there would be more whole-genome sequencing on Illumina technology complemented with use of the Sequel to get an "in-depth look at structural variants" and "bits of the genome that short-read technology can't get, like the HLA regions, repetitive elements, and centromeres."
In addition, due to the long reads' advantages in looking at structural variation, "I think people will now start sequencing cancer genomes on the Sequel," he added.
However, the success of the Sequel will depend on the quality of the data, noted Chad Nusbaum of the Broad Institute, none of which has yet been made publicly available.
In addition, as Oxford Nanopore continues to improve its nanopore sequencing technology, it may steal some of PacBio's thunder. "They're in a bit of a dog fight," Watson said, adding that competition in the long-read space is a good thing.
Oxford Nanopore delivers
Oxford Nanopore launched its early-access program for its MinIon nanopore sequencer last year. Since then, the program has expanded and groups have published numerous studies demonstrating the instrument's potential to aid in genome assembly and to sequence microbial genomes and environmental samples quickly and outside the standard laboratory.
Researchers at the NASA Johnson Space Center are planning to take a MinIon to space in 2016 to sequence samples on board the International Space Station. Eventually, some researchers think it could be used for point-of-care testing — such as a rapid test to diagnose an unknown infection — and real-time outbreak analysis, for instance, in the case of the West African Ebola outbreak.
"There's real enthusiasm for what's coming" from Oxford Nanopore, Hadfield told GenomeWeb. "There were a lot more data and publications this year showing that the technology does, in fact, work and that it can be used for interesting research."
Whether Oxford will overtake PacBio still remains to be seen. "PacBio has a customer base and a proven technology," Watson said. The MinIon and forth-coming PromethIon are still developing, but Oxford's technology has the potential to "blow everything out of the water."
BGI's about face
BGI announced the launch of a high-throughput sequencer based on Complete Genomics' technology called Revolocity in June. At the time, Complete Genomics CEO Cliff Reid said the instrument had the capability of sequencing 10,000 human genomes per year, putting it on par with Illumina's HiSeq X Ten. The company had also secured three customers — Radboud University Medical Center in the Netherlands, Mater Health Services in Australia, and the Epilepsy Society in the UK — although BGI hadn't planned to ship instruments to customers until the first half of 2016.
But, in November, BGI put commercialization of the system on hold. GenomeWeb also learned that Reid would resign as CEO of Complete Genomics, and that BGI would focus its efforts on its desktop sequencer, BGISEQ-500, which it plans to bring through the China Food and Drug Administration. The shift came following the departure of Jun Wang, former chief executive of BGI, who had been with the institute since its founding 16 years ago.
Watson speculated that Revolocity may have turned out to be too complex of an instrument for commercialization. "It looked like a complex machine, and even the sequencers that are easy to run break down often," he said.
Nusbaum also noted that the "abrupt change" was a shame, but did not know why BGI made its decision.
Looking ahead to 2016, researchers are excited about advances in single-cell technologies, the potential for 10X Genomics' technology, and the potential availability of genomic data from large-scale population sequencing projects.
"I think that we're in the middle of very rapid technological progress with respect to front-end methods for capturing, compartmentalizing, and tagging information that tells us what reads are coming from the same cell," Shendure said. That includes advances by 10X Genomics, droplet-based methods like Drop-Seq that rapidly profile thousands of single cells, as well as technology that Shendure's lab has worked on, CPT-seq, to create thousands of labeled DNA pools.
Hadfield also noted developments in the area of single-cell genomics and genome phasing and automation on the front-end of NGS. "These enabling technologies, which allow us to conceive of more complex experiments, is where I'd like to see the next revolution," he said.
More clinical sequencing is also in the works. "The regulatory challenges are increasingly apparent to everyone," Shendure said, "but there's good faith on all sides to do this in a way that's best for the patients, and I can't imagine that things won't continue to progress" in 2016.