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In Sequence 2013 Survey: Illumina Pulls Further Ahead, Interest in Oxford Nanopore Remains High

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An end-of-year sequencing survey of GenomeWeb readers reveals that Illumina has solidified its dominant market position in next-gen sequencing over the last year.

The overall picture holds true for the clinical sequencing market as well, assessed for the first time this year, where Illumina's leadership is even more pronounced.

When it comes to purchasing plans, Illumina is rivaled by Oxford Nanopore Technologies, which recently started an early access program for its first commercial platform.

In addition, the majority of survey responders expects the next big technology advance in sequencing to come from Oxford Nanopore, followed by Illumina and Pacific Biosciences.

The survey, In Sequence's 6th annual assessment of the next-generation sequencing market, was conducted in late December in collaboration with investment firm Mizuho Securities, which analyzed the data. Questions were sent out via e-mail to a subset of GenomeWeb's readership. One hundred and forty-nine readers completed the survey in full or in part, of which 121 said they currently use next-gen sequencing.

About two-thirds of respondents have at least one MiSeq, and more than half own at least one HiSeq, illustrating Illumina's market leadership. About two-fifths have at least one PGM, and 12 percent at least one Ion Proton, both of which are sold by Life Technologies' Ion Torrent. Approximately one-fifth each own a Roche 454 system or at least one PacBio RS, about 10 percent have at least one Illumina Genome Analyzer, and fewer than 10 percent own one or more Life Tech SOLiDs.

Based on an estimate of the number of sequencing systems owned by survey participants, llumina holds about 70 percent of the overall market, gaining slightly at the expense of its competitors compared to our 2012 survey. Life Technologies lost 8 percentage points of its market share, which now stands at 16 percent, while Roche and PacBio shares held pretty much steady, at 10 and 3 percent, respectively (see charts).

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Almost half of sixty-two participants who are considering adding a next-gen sequencing instrument this year said they would opt for Oxford Nanopore Technologies' MinIon, and 45 percent for a GridIon, demonstrating users' considerable interest in the first nanopore sequencing platform to reach the market. Oxford Nano started an early access program for the MinIon late last year but has not said when it will commercialize the GridIon. In 2012, about a quarter of respondents were considering purchasing either of the Oxford Nano systems, which were not available at that time (see chart).

About 40 percent of respondents said they were considering purchasing a MiSeq, and 40 percent a HiSeq, a slight increase over last year, when 35 percent were thinking about a MiSeq, and 33 percent about a HiSeq.

The Ion Proton is the top choice for 21 percent of respondents, a marked decline from last year, when 35 percent were considering the platform.

About 15 percent are considering the PacBio RS, compared to last year, when only 1 percent were doing so, showing that users have gained more confidence in the platform and its applications.

Thirteen percent are considering the MiSeqDx, which was not available last year, and 13 percent the Qiagen GeneReader, which the company plans to commercialize this year. One participant each said they are thinking about getting a PGM, a SOLiD, or a GnuBio system, which is also expected to be released this year.

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Thirty-two survey responders said they retired or traded in a sequencing system over the past year. Among the 45 discontinued systems, about a quarter were 454 machines, another quarter Illumina Genome Analyzers, and a fifth Life Tech SOLiD systems, reflecting the rapid succession of these platforms by newer technologies. But other platforms were affected as well: 9 percent of respondents retired a HiSeq machine, 7 percent a PGM, and 4 percent a MiSeq, while a single user discontinued an Illumina HiScanSQ, and another one a capillary sequencer (see chart).

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Providing the next big leap

Asked which company's technology will provide "the next big leap" in sequencing, half of 75 respondents said they put their faith in Oxford Nanopore Technologies, even though the company has not publicly shown any sequencing data yet.

A quarter said that Illumina will provide the next big technology advance, followed by 20 percent betting on Pacific Biosciences, 12 percent on GnuBio, 11 percent on Ion Torrent, 8 percent on Qiagen, 7 percent on Genia, and 3 percent on GenapSys.

Sixteen percent of respondents had either no opinion or did not think any of these choices were appropriate, and none wrote in a technology developer that was not on the list.

Clinical sequencing

Of 27 responders who currently perform clinical or diagnostic sequencing, about half currently use the Illumina MiSeq and half use the HiSeq, underscoring Illumina's dominant position in the clinical sequencing market. Twenty-two percent use the Ion Torrent PGM, and a single responder each uses one of the 454 platforms, the PacBio RS, or the Ion Proton. Capillary electrophoresis, or Sanger, sequencing is used by about 10 percent of respondents for clinical sequencing.

When asked what systems they are planning to bring in for clinical sequencing over the next year, if any, about a quarter mentioned the MiSeq or MiSeqDx, a fifth the HiSeq, and about 15 percent each opted for the PGM or the Ion Proton. A single user each is planning to add a 454 system, a PacBioRS, and a capillary electrophoresis sequencer.

Last year, Illumina was the first company to gain 510(k) (chk) approval from the FDA for a next-gen sequencing system, the MiSeqDx, after obtaining a CE mark for the system earlier in the year. However, our survey participants do not seem to value this much: More than half of 26 responders said an FDA-approved or CE-marked next-gen sequencing system would be "nice to have but not crucial," and about a third regard such a feature as "not important," while only 15 percent said it was "very important."

Sequencing applications

Users varied in the use of their sequencing systems. The dominant applications for the HiSeq are whole-genome sequencing and RNA-seq/transcriptome sequencing (each 76 percent), reflecting that system's high throughput, followed by exome sequencing (68 percent) and targeted/amplicon sequencing (65 percent) (see chart – data only available for HiSeq, MiSeq, and PGM).

For the MiSeq, the main application by far, for 79 percent of users, is targeted/amplicon sequencing, followed by microbial genome sequencing (64 percent) and RNA-seq/transcriptome sequencing (61 percent).

PGM users, likewise, use their system overwhelmingly for targeted/amplicon sequencing (80 percent), with microbial genome sequencing a distant second (35 percent).

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Only five users of the Ion Proton provided information about their use of the system – three users mentioned targeted/amplicon sequencing, and two each put down whole-genome sequencing, exome sequencing, and RNA-seq/transcriptome sequencing.

PacBio users mentioned whole-genome de novo sequencing as the primary application (63 percent), followed by microbial genome sequencing (56 percent), methylation sequencing, and targeted/amplicon sequencing (each 50 percent).

Users of the 454 GS FLX or GS Junior systems mentioned targeted/amplicon sequencing as their most prominent application (82 percent), followed by metagenomic sequencing and whole-genome de novo sequencing (each 36 percent).

Meeting expectations?

Users varied in how satisfied they are with their sequencing platforms regarding a number of metrics, compared to the expectations they harbored for the instrument. Categories assessed were instrument price, reagent price, ease of sample prep, throughput, output per run, run time, accuracy, read length, ease of data analysis, amount of uptime, reliability, and satisfaction with service, and users chose between above expectations, below expectations, and neutral.

More HiSeq customers said their expectations were exceeded rather than not met in terms of throughput, output per run, accuracy, and satisfaction with Illumina's service. But the instrument price, reagent prices, and run time came in below expectations for more users.

MiSeq users were largely satisfied with their platform, with more saying it performed above expectations than below expectations in all categories except for instrument and reagent price.

Users of the PGM were generally less satisfied with their system, with more users stating the platform performed below rather than above expectations in all categories except run time and instrument price.

System stability

A number of users had trouble with their sequencing systems over the last few months. More than half of HiSeq users said they had experienced a problem, the majority related to hardware, and almost half of PacBio RS users reported problems with their machine, half related to hardware and a third to software.

More than two-fifths of Ion Proton users said they had issues, too, half of them with consumables, and almost two-fifths of MiSeq users reported a problem with their system, about half related to hardware.

About a quarter each of Genome Analyzer, PGM, and 454 users also mentioned problems with their systems. A single user reported an issue with the SOLiD system.

Demographics

Around two-thirds of survey respondents were from North America, about a quarter from Europe, and 10 percent from Asia and Australia.

Three-quarters of participants work in the non-commercial sector: 42 percent at a university or non-profit research institute, 19 percent at an academic medical center, and 14 percent at a government lab or agency. On the commercial side, 14 percent work for an instrument or reagent manufacturer, and 8 percent for a service provider.

Seventy percent of respondents employ NGS in basic research, 43 percent in clinical or translational research, 35 percent in clinical diagnostics, 7 percent in food or environmental safety testing, 3 percent in forensics, and the remainder in other areas, including ag-bio and service work.

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