Tech Review

“It’s going to be the PC for biologists”

01.02.2010

The market share of ultrafast sequencing machines on the total sequencing market is set to expand rapidly. In April 2010, Roche daughter 454 Life Sciences (Branford, US) is launching a new system especially designed for individual researchers. The size of a laser printer, the machine has read lengths of 400-500 base pairs and will be sold at a fraction of the cost of other current high throughput sequencing systems. 454’s GS Junior addresses a market that is estimated to be 10-100 times larger than that for the current US$500,000 machines, which are aimed at just 1,000 core labs and sequencing centres worldwide. The new development looks set to make next-generation sequencing available even for smaller labs. EuroBiotechNews spoke with Christopher McLeod, President and CEO of 454 Life Sciences, about what the new system can do.

The market share of ultrafast sequencing machines on the total sequencing market is set to expand rapidly. In April 2010, Roche daughter 454 Life Sciences (Branford, US) is launching a new system especially designed for individual researchers. The size of a laser printer, the machine has read lengths of 400-500 base pairs and will be sold at a fraction of the cost of other current high throughput sequencing systems. 454’s GS Junior addresses a market that is estimated to be 10-100 times larger than that for the current US$500,000 machines, which are aimed at just 1,000 core labs and sequencing centres worldwide. The new development looks set to make next-generation sequencing available even for smaller labs. EuroBiotechNews spoke with Christopher McLeod, President and CEO of 454 Life Sciences, about what the new system can do.

Euro|BioTech|News
Roche/454 recently announced it was launching the GS Junior System – a new machine for next-generation sequencing – by the spring of 2010. What are its features and its target markets?

McLeod:
With the GS Junior, we will make next-generation sequencing available to the indi-

vidual researcher. Up to now, access to high-throughput sequencing was still primarily limited to large research facilities because of IT infrastructure requirements for data analysis, and the cost of capital equipment and disposables. We want to change that with a new system that is tailored to the needs of the individual lab. The GS Junior is a benchtop system that offers a throughput of over 35 million high-quality, filtered bases per run – which is about 100,000 reads. The system needs 10 hours for sequencing, and an additional 2 hours for data processing. Like its big brother, the GS FLX System, it will offer read lengths of 400 base pairs on average at 99% accuracy. All 454 data processing can be performed on an accompanying computer with a pre-installed software package that includes easy-to-use tools for assembly, mapping and variant detection. We will launch our new system by March or April 2010.

Euro|BioTech|News
What was behind the idea to bring this kind of personal sequencer to market?

McLeod:
DNA sequencing has become more affordable with the introduction of 454 sequencing and other high-throughput sequencing technologies. We are continuing to try to improve the performance of our technology, including our flagship system the GS FLX system – to increase the throughput and reduce the cost per base of sequencing. Recently, we announced that we will double the read lengths of our current GS FLX Titanium Chemistry kits from 400-500 bp per read to 800-1000 base pair reads in 2010, which is comparable to that of Sanger sequencing. In terms of throughput, we are far beyond Sanger sequencing because of its 500 times faster throughput and reads that are 50 times cheaper. One of the strongest applications of 454 Sequencing systems is analysing genes or genetic regions in great depth – whether to identify rare mutations such as in HI-Viruses, or to identify haplotypes within the MHC region, which includes a critical set of genes involved in immune response. However, the capabilities of the current GS FLX System are often too great for this type of research. You don’t need to have a US$500,000 instrument and a US$5,000 run cost if your goal is to analyse a limited number of genes. So what we have heard from our customers is that they would like a less expensive instrument; one that doesn’t need the same throughput, but is significantly less expensive per run. We have delivered on these needs with the GS Junior System. This new system is truly targeted for the benchtop in the individual lab, as opposed to core labs or genome centers. With the GS FLX we revolutionised sequencing. Five years ago, high-throughput sequencing was really only being done in 10-12 genome centers, because it required tens of millions of dollars of investment to have the kind of throughput that you would need. With our GS FLX System, you can achieve this level of sequencing power with a single instrument. So now high-throughput sequencing has expanded in many more labs, such as core labs. But now with the GS Junior System, we want to become for biology what personal computing has been for the IT branch. It really is an individual piece of research equipment.

Euro|BioTech|News
According to your estimates, how many additional customers does it address?

McLeod:
Our GS FLX System targets a market of perhaps 1,000-2,000 customers worldwide. In comparison, our new GS Junior System, which costs one fifth of the price, targets all the tens of thousands of labs that have, for example, a thermocycler. It targets all research groups that carry out targeted sequencing for identifying genomic regions that are associated with disease, all groups that carry out genotyping or de-novo microbial genome sequencing, as well as those pursuing metagenomic studies or seeking to detect novel pathogens.
Euro|BioTech|News
What are the advantages of Roche/454’s two sequencing systems compared to the systems offered by Illumina and ABI/Life Technologies? What do you predict for its market position in applications such as re-sequencing, de-novo sequencing, transcriptional profiling, miRNA sequencing, amplicon sequencing, and so on?

McLeod:
GS Junior will target the scientist in the individual lab. Whether or not our competitors decide that this is a market they want to address – and whether or not their technologies will scale as well – is an open question. Comparing the GS FLX with the offerings from Illumina or the ABI SOLID system, their systems are capable of generating more bases with a larger number of reads, but significantly shorter read lengths. The strength of our technology is in applications that require long, high-quality reads. This includes almost every type of de-novo assembly; i.e when you are sequencing an organism for the first time and building a reference sequence, searching for the presence of rare variations in viruses, or if you want to identify which organisms are present in metagenomic analyses. On top of this, we think that our system has some very clear speed and data analysis advantages. Because you can complete a sequencing run in less than 12 hours with 454 sequencing, researchers can get results very quickly. Our competitors need days, if not weeks to generate results. Secondly, what really is becoming the bottleneck now is not the sequencing itself, but how to analyse the data at an acceptable cost and then to transform the data into useful , biologically-relevant results.

Euro|BioTech|News
The GS Junior has a kind of automated assembly software for users who are unfamiliar with bioinformatics. Can you give us some details about that feature?

McLeod:
That feature is part of the overall software design. Whether the task is to assemble a whole genome sequence de novo or to look at genomic variation caused by SNPs, deletions, copy number variations or genomic re-arrangements, in both cases we have software tools that will make it easy for the GS Junior user to go from experimental design to analysis of the data. Another point is that if you are going to resequence a genomic region, what you are doing is mapping against a reference genome. The problem you run into is that you may miss certain types of variations because you are forced to map against a reference. We think that certain experiments need to use de-novo assembly. And we provide an automated solution to do this with our GS De Novo Assembler software.
Euro|BioTech|News
What advantages does the GS Junior offer compared to the GS FLX System?

McLeod:
The benefit of the GS Junior System is that it is a much more affordable solution. It can be acquired by individual scientists, and give very quick answers to research questions. In comparison to the GS FLX, the GS Junior System has a lower throughput – but the cost per run and the instrument cost is lower.
Euro|BioTech|News
What research applications is the the new system designed for?

McLeod:
The system is sized for a number of different applications. If you wanted to analyse drug resistance in HIV in the past, and do it economically, you would need to run 40 or 50 samples at a time. With the GS Junior, you can do the same analysis economically with 10 samples, without the need to wait for enough samples to perform a sequencing. For certain types of research, you don’t need the full throughput of the GS FLX. This is also true if you’re looking at certain genes for potential genetic disease, which you can do with a handful of samples, depending on the experimental design. As mentioned before, the system is also capable of sequencing whole viral or microbal genomes de novo in a single run. You can also use the system for research into individual bacterial genomes.

Euro|BioTech|News
Currently, the GS FLX as well as the GS Junior are for research use only. When will we see systems approved for use in the diagnostics market?
McLeod:
We are speaking with regulatory authorities and experts in the US and in Europe about what is required to bring a system into that market segment. The GS FLX System is already used in research to identify bio­markers. Now we want to see it approved for use in diagnostics because there is tremendous interest amongst our customers.

Euro|BioTech|News
Have next-generation sequencers already replaced Sanger sequencers, or will these continue to have a significant market share?

McLeod:
What we can see about the impact of high throughput sequencing from ABIs financials is that there is still a substantial market for Sanger sequencing. However, we think that this will erode, as the capabilities of the high-throughput platforms are better suited for more and more applications. Nobody can predict if they will be completely eliminated, but the GS Junior and the GS FLX Systems will replace Sanger sequencing where they offer clear advantages to customers, as in de-novo sequencing. In terms of the current market share, there are estimates that more than half of the total sequencing market is being covered by new-generation high-throughput sequencing. But it is difficult to extract the exact numbers from our competitors.

Euro|BioTech|News
There have been several announcements of single molecule sequencing platforms. How far along are they?

McLeod:
Collectively, the risk that most single molecule approaches have is that you only have one chance to record a base, and if you miss it you could have an error. What we have seen so far is Helicos, with the only single-molecule platform that is commercially available. They tend to compete more with the Illumina and the SOLID platforms, but because they lack the read length quality for de-novo sequencing, an application in which 454 Sequencing remains unmatched, were not able to carry out high-throughput de-novo sequencing.

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