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Next-Generation Sequencing Hype Confirmed

Perhaps the most buzz-worthy technology in life sciences, next-generation sequencing continues to undergo rapid changes. With vendors updating their portfolios with new instruments annually, the market remains highly competitive and dynamic.

by Christi Bird

Survey Finds Adoption Remains Robust

Perhaps the most buzz-worthy technology in life sciences, next-generation sequencing continues to undergo rapid changes. With vendors updating their portfolios with new instruments annually, the market remains highly competitive and dynamic. The editors of Lab Manager and Frost & Sullivan recently conducted a survey to better understand the sequencing end-user base. A total of 79 Lab Manager Magazine readers qualified for the survey as current or future users of sequencing technology, representing research and clinical laboratories, core facilities, sequencing services providers, and major genomes centers globally.

Sequencing adoption

Since the advent of the next-generation sequencing market in 2005, several vendors have developed new technologies and delivered multiple updates of their systems. With these instrument releases, throughput, run time, and the cost per genome have dramatically improved. The highest throughput instruments currently boast throughputs of over 200 gigabases (Gb) of data per run, with a cost per genome under $10,000.

Capillary Electrophoresis (CE) Sanger sequencing systems remain entrenched in laboratories, with over half of respondents owning an average of two instruments. Of next-generation sequencing platforms, Illumina holds the highest percentage of instrument adoption, with 25 percent of respondents owning one or more of the company’s instruments. In particular, the company’s HiSeq 2000 has the greatest adoption amongst respondents, with 14 percent reporting installed instruments. Life Technologies, who offers the SOLiD™ technology and Ion Torrent’s Personal Genome Machine™ (PGM) accounted for the second-most popular next-generation provider, with 20 percent of respondents utilizing the company’s systems. Roche 454 Life Sciences, provider of the long-read GS FLX and GS Junior platforms, followed closely with 18 percent of users currently owning a system. These results confirm general market knowledge that Illumina, Life Technologies, and Roche 454 remain the top three sequencing instrument providers. Illumina’s and Life Technologies’ high throughput instruments remain the workhorses of large genome centers, while Roche is best suited for targeted, long-read applications.

According to the survey, Life Technologies and Illumina may realize similar gains in adoption over the next two years, as 32% and 28% of respondents, respectively, expressed intention to purchase their instruments. Roche may see double-digit growth in adoption as well, with 18% of users expecting to purchase one of the company’s long-read platforms. The most popular Life Technologies instruments for future purchase are the Ion Torrent PGM™ with 19% of respondents planning adoption, followed by the SOLiD™ 5500xl or 5500 with 16% planning to install an instrument. Of Illumina’s platforms, the MiSeq is most popular with respondents in the future, with 18% planning to install the instrument in the next two years. Overall, researchers cited throughput, speed, and instrument price as the top three reasons for their instrument purchases.

The recent vendor trend of launching affordable, easy-to-use, “personal” genome sequencers appears it will pay off for sequencing providers. The Ion Torrent PGM, Illumina MiSeq, and Roche 454 GS Junior were selected by 19%, 18%, and 15% of respondents, respectively, as their future instruments of choice. Researchers planning to purchase these “personal” platforms cited speed, instrument cost, and ease-of-use as the three main reasons for selecting these instruments. Thus, these users are more interested in simplicity than throughput needs compared with overall results. Sequencing developers first launched these low-to-mid throughput small footprint instruments in 2010 at lower price points than full systems. These sequencers feature lower outputs, often half the Gb of data per run of their more expensive counterparts. Vendors are marketing these instruments at smaller laboratories without large capital equipment budgets to purchase high throughput systems, or labs that simply conduct smaller-scale projects that require targeted sequencing. The ease-of-use of these instruments allows novice sequencing users to acquire a system and begin work immediately without in-house expertise. Ultimately, these new platforms aim to secure a wider customer base for a technology previously considered too challenging without training. According to the survey, researchers are enthusiastic about these platforms and plan to acquire them more readily than high throughput systems.

The use of core facilities or sequencing services providers remain readily available options for researchers wishing to utilize the technology, but either lack a sequencing instrument in-house or wish to outsource for throughput, timing, or other needs. An expanding marketplace of vendors offer various sequencing services, including whole genome sequencing, and specialty applications such as RNA-seq, ChIP-seq, microRNA discovery, and DNA methylation sequencing. Service providers range in size, capacity, and focus. Examples of providers include Illumina, Complete Genomics, Beijing Genomics Institute (BGI) Americas, Expression Analysis, LC Sciences, Knome, and Array- Star, to name a few. To view the tremendous growth in this market, one needs only to look at the financials and expansion plans of recently public Complete Genomics. After finishing 2010 with total annual revenues of $9.4 million, the firm announced revenues of $6.8 million for the first quarter of 2011 alone.

Our survey confirms that outsourcing sequencing remains a popular option amongst researchers. Of respondents, 36% currently outsource their sequencing work, with an additional 20% planning to outsource within the next two years. The remaining 44% expressed no plans to outsource now or over the next two years. Asked what platforms they prefer to be used for their current or planned outsourced sequencing work, around 40% favor capillary electrophoresis sequencers. Of next-generation sequencers, Illumina’s GA Analyzer IIx, HiSeq 2000, and MiSeq platforms are preferred equally at 11% each for researchers’ current outsourcing efforts. Ion Torrent’s PGM and Roche 454’s GS/FLX are other popular platforms of respondents planning to outsource over the next two years.

Despite these statistics showing clear platform preferences of sequencing outsourcers, researchers often have little choice over the instruments their core facilities use. In addition, the majority of non-university based providers offer sequencing services on Illumina platforms, which may bias outsourcers. These companies often compete on price, convenience, and expertise in niche applications, which may have stronger influences on researchers’ provider preference than the sequencing platform used. In fact, many services providers express that researchers care mostly about the biological questions they wish to answer and less about the way their outsourcing providers get to those answers. Thus, instrument preferences of researchers with sequencing platforms in-house are stronger indicators of reputation and market success than outsourcing choices.

While most of the sequencing platform providers offer accompanying consumables for their instruments, a multitude of additional companies provide reagents for this rapidly growing field. According to the survey, however, researchers often use consumables provided by the sequencing instrument vendors. Asked to choose their preferred providers of sequencing consumables, respondents selected Life Technologies (Applied Biosystems), Illumina, and Roche (454 Life Sciences) as their most-utilized vendors. Thermo Fisher Scientific and Agilent, companies without sequencing instrument portfolios, rounded out the top five. Over half of respondents ranked Life Technologies (including Applied Biosystems) as their most preferred provider, citing quality, price, reliability, ease-of-use, and service as main reasons they remain loyal customers of the company’s sequencing consumables.

Sequencing budget

Respondents were asked about their 2010 and 2011 budgets for sequencing instrumentation, consumables, and storage/bioinformatics. Nearly half of respondents have a 2011 budget for sequencing instrumentation between $0 and $250,000, while 19% reported budgets greater than $250,000. Overall, respondents reported their budgets for sequencing instruments increased 3% from 2010 levels. For sequencing consumables, budgets between $0 and $50,000 are the most common in 2011, with half of respondents reporting these figures. Consumables budgets are up 4% from 2010 amounts. Most respondents have a 2011 budget for sequencing storage and bioinformatics less than $10,000. A surprisingly large 30% of respondents expressed that they are unaware of their sequencing storage and bioinformatics allotments, suggesting these budgets may be handled by separate decision makers. Those respondents with knowledge of their 2011 storage and bioinformatics budget reported an average increase of 6% from 2010 amounts. These modest budget increases for sequencing tools reflect the rather stagnant state of scientific funding. Since the drying up of funds from the American Recovery and Reinvestment Act (ARRA) of 2009, funding levels have remained relatively flat. Given that the National Institutes of Health mandated that ARRA grant money be used swiftly within the first two years of funding, thus by the end of 2010, it is a testament to the enthusiasm surrounding sequencing that 2011 budget levels increased.

2011 Budget for Sequencing Instrumentation (N=79)

With the launch of affordable “personal” genome sequencers, researchers no longer need to seek instrumentation grants or budgets of $0.5 million in order to adopt sequencing. In addition, once the desired infrastructure of sequencing instruments is met, laboratories require considerably lower instrumentation budgets for upgrades. While these actions may serve to lower instrumentation budgets, it is clear that next-generation sequencing remains in a strong adoption period with market saturation far from met. With several new platforms entering the market each year, researchers can increasingly find the instrument that fits their throughput, complexity, speed, and application needs. Thus, a rapidly expanding enduser base remains the main driver to this dynamic market. While the consumables volume requirement and price to sequence a genome continue to drop due to greater workflow efficiency, the expanding user base and increasing number of projects and applications enabled by sequencing will offset these reductions in reagent costs.

Sequencing applications

As sequencing instruments improved, researchers and providers diligently developed new applications that could be performed with sequencers. Respondents were provided a list of 29 different applications that ranged from whole genome to targeted analysis, disease-based research, epigenetics, RNA-based studies, diagnostics, and forensics studies. Selecting the applications currently conducted at their laboratories, the most popular proved to be SNP analysis, RNA Seq/transcriptome sequencing, and targeted/amplicon/exome sequencing, with 35%, 33%, and 33% of respondents respectively conducting these types of analyses. Knowledge of the most popular sequencing applications may help instrument, consumables, and software providers optimize their products for the most widely-conducted analyses.

Conclusion

Despite rapid improvements made to sequencing platforms over the past five years, challenges with the technology still exist. According to respondents, the most significant challenges when using sequencing technologies are the high cost per sample, data storage and management, and analytical tools and informatics. Platform providers and sequencing services vendors continue to work diligently on decreasing the cost of sequencing a genome. Several systems currently boast costs per genome of $5000, while sequencing services providers are reportedly nearing in-house costs of less than $2000. The market continues to strive for the $1000 genome, a 10-year goal set by the National Institutes of Health in 2004 with grants funded to a broad range of sequencing technology development efforts. Given the current pace of annually releasing new systems with improvements to speed, cost, and throughput, it is highly likely the $1000 genome will be met within the next two years.

As expected, the survey indicated sequencing instrumentation remains in a strong adoption and growth period. Results revealed that “personal” genome sequencers, new to the market in 2010, are rapidly becoming a popular choice amongst researchers. These instruments will serve to significantly expand the next-generation sequencing end-user base over the next two years. Outsourcing of sequencing work also remains a viable option for researchers, as over half of respondents currently use or plan to use such services in the short term. Furthermore, budgets for sequencing instrumentation, consumables, and storage, and bioinformatics remain strong, on average increasing 3% to 6% from 2010 to 2011. However, despite rapid and dramatic improvements to sequencers, challenges still exist for researchers using the technology, most importantly in cost per genome and bioinformatics and analytical issues. Nevertheless, it appears these challenges are not significantly delaying instrument adoption, or technology enthusiasm. Now in the third decade of genome sequencing technology, the expansion of product options and the decreasing cost and speed to sequence a genome are enabling this cutting-edge technology to form a growing end-user base and ultimately advance biomedical research.