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Illumina's Proposed PacBio Acquisition Leaves Customers Cautiously Optimistic


SAN FRANCISCO (GenomeWeb) – Following last week's announcement that Illumina plans to purchase Pacific Biosciences for $1.2 billion, next-generation sequencing customers say the acquisition could potentially benefit the NGS field, though they also have concerns about the impact of reduced competition.

For the most part, users appear optimistic that the acquisition would spur development of PacBio's single-molecule sequencing technology and are curious about the potential integration of PacBio's and Illumina's technologies.

Nonetheless, some users expressed concern about further consolidating the NGS market into Illumina's hands and thought that competition from Oxford Nanopore Technologies would be critical.

Shawn Levy, director of the genomic services lab at the HudsonAlpha Institute for Biotechnology, which has Illumina, PacBio, and Oxford Nanopore platforms installed, said that while a worst-case scenario would involve Illumina stalling innovation on long-read sequencing, "that hasn't been something they've tried to do in the past, so it would be very surprising if they took that tack."

One major advantage resulting from the acquisition, users noted, is that it would provide additional resources for PacBio, which has had some financial struggles over the years. In 2011, for instance, it had to lay off around a quarter of its workforce, and although it has continued to make improvements to its technology, it often misses expectations for instrument sales and is not profitable.

PacBio's limited resources "put a ceiling on how far they could take the technology," said Mike Schatz, an associate professor of computer science at Johns Hopkins University who uses both PacBio and Oxford Nanopore's platforms.

Illumina's resources could help make the PacBio technology scalable and "ultimately, more practical to deploy in clinical settings," he said.

While PacBio's single-molecule sequencing technology "has been much appreciated by the PacBio user community, that's only a relatively small number of specialized labs," said Adam Ameur, associate professor at Uppsala University, who has developed sample prep techniques for both PacBio's and Oxford Nanopore's technologies.. But with the weight of Illumina behind it, Ameur anticipates that the user base would grow. "This is likely to accelerate the use of long reads both for research and clinical diagnostics," he said.

Chia-Lin Wei, director of genome technologies at the Jackson Laboratory, which has Illumina, PacBio, and Oxford Nanopore technologies, agreed that the additional resources from Illumina could help speed development of the PacBio technology. While PacBio has made updates in recent years, the improvements have been slow, she said, adding that "with Illumina behind it, I think PacBio will be able to roll out the upgrades more quickly."

In addition, "Illumina has a track record in engineering instruments, rolling out new improvements and upgrades to sequencing chemistry, and making platform improvements," she said, "so it will be good if they can bring that expertise to the PacBio platform."

The timing of the acquisition announcement was also important, Levy noted. "The scientific impact of long-read sequencing technology has been tremendous over the last few years and especially this last year," he said. For instance, a number of groups have reported on the benefit of using long reads identify pathogenic structural variants, target repeat expansions, and identify breakpoints in complex genomic rearrangments.

Wei said that the proposed acquisition also helps validate the field of single-molecule long-read sequencing. "Long reads have some distinct advantages, so it's good to see that Illumina is now moving aggressively into this field," she said.

Nonetheless, "there's some concern about [Illumina] having a monopoly," she said. Although Illumina's short-read technology can be considered complementary to PacBio's single-molecule sequencing technology, the acquisition could potentially have an impact on Oxford Nanopore Technologies, for example.

Wei said she thinks, though, that Oxford Nanopore would continue to be competitive. For one thing, she said, the company has a different model. Rather than targeting large genome centers, it has "encouraged a lot more users from different fields and types of applications and those users are readily adopting the technology," she said. "I don't think the acquisition will slow Oxford Nanopore down, and in fact, I'm hoping it will inject new energy into them to make sure the field maintains its excitement with using long-read technology."

Ameur, despite being "a little worried about the competition in the sequencing market," agreed with Wei that Oxford Nanopore would continue to be an important player in the single-molecule sequencing space.

The technology "has some unique features and a somewhat different user base compared to PacBio," he said. For instance, some users have reported generating read lengths of up to 2 megabases using Oxford Nanopore's technology, which  "far exceeds the current lengths obtained by PacBio," he said. "There are also some unique applications, such as direct sequencing of RNA," that can only be done with nanopore sequencing at the moment.

In addition, he said, now that Oxford Nanopore has launched its PromethIon system, it is more competitive on both throughput and cost per base, and it would continue to keep the pressure on Illumina and PacBio to reduce their costs.

Schatz said that one potential downside for Oxford Nanopore would be the sheer brand recognition of Illumina, which could convince new users to choose PacBio technology over Oxford Nanopore's. "It will be a race for the next five years to see which technology will be dominant," he said. "Both PacBio and Oxford Nanopore are on exciting growth paths, which ultimately will be good for customers."

Oxford Nanopore declined to comment for this article.

Another potential impact of the acquisition is on linked-read technologies and long-range genome mapping technologies, like the one developed by 10x Genomics and Bionano Genomics. Wei said that the linked-read sequencing field has not progressed much and that there has not been enough development of computational tools to support the technology.

Schatz, however, thought that linked reads would continue to have their own niche, for instance in phasing.

For its part, 10x Genomics is optimistic about the deal. CEO Serge Saxonov said in an email that the acquisition is "great for the sequencing market as a whole and validation that long-range information is important." He said that as long reads become more accessible and cost effective, the firm sees "additional opportunities [to develop] more applications" in that space.

Bionano Genomics also believes there will still be room other genomic technologies that deliver long-range information. In a conference call to discuss the company's earnings this week, CEO Erik Holmlin said that the firm's Saphyr genome mapping platform delivers information that Illumina and PacBio cannot. "Saphyr sees variants these systems miss," he said. "We remain perfectly complementary to those tools."