Catching the wave of large-scale human genome sequencing early on, GATC Biotech said this week that it is now offering a human genome sequencing service.
The German sequencing and bioinformatics service provider said it has had requests for such services from academic researchers, and hopes that industry customers will follow. The service, which will be available immediately, mostly employs new sequencing technologies. The company estimates that after expanding its staff and adding equipment, it will be capable of sequencing up to 100 human genomes within the next three years.
Also this week, GATC expects to receive an ABI SOLiD sequencer, adding to the Illumina Genome Analyzer and the 454 FLX that the company brought in house earlier this year, as well as to an undisclosed number of 3730xl Sanger sequencers. GATC announced this summer that it would install the SOLiD in the fall and start offering services on the machine by the end of this year (see In Sequence 7/31/2007).
“We feel that we are, with our four leading sequencing technologies, equipped to go into producing human genome sequences,” GATC CEO Peter Pohl told In Sequence last week.
But what exactly “producing a human genome” means will be determined by the customers. “We would turn the question over to the customer and first ask, ‘What do you need it for?’” said chief operating officer Marcus Benz.
For example, while some users would merely want “a glimpse on the variation of DNA structure,” others would like to focus on specific regions of the genome in greater detail. “This influences the strategy of the approach,” he said.
In general, GATC plans to start with paired-end reads across the genome using short reads that Illumina’s and ABI’s systems provide. Depending on the project, the company might also select certain regions, employing one of the recently published capture technologies (see In Sequence 11/6/2007), and sequence these “probably with longer reads” from 454’s platform. Sanger reads might be added to improve the data quality in specific regions of the genome.
The company will not generate de novo assemblies but will map the reads back to existing human genomes.
Project costs could range from €50,000 ($73,000) for 1-fold coverage to more than €1 million ($1.5 million) “if you want to have a medically usable dataset,” according to Pohl.
On average, he expects that if his company delivers 100 genomes in the next three years as planned, the cost per genome would average €400,000 to €500,000. At the moment, that would yield 5-fold to 10-fold coverage, based on a mix of new sequencing technologies, according to Benz.
So far, GATC has not yet proven that it can sequence and analyze full human genomes. In the past, it has sequenced eukaryotes that are a fraction the size of a human: the 30 megabase fungus Aspergillus niger, using Sanger technology; and an undisclosed large fungus for a large industrial customer using next-generation technology. The company is also currently a major sequencing provider for a 840-megabase potato sequencing project, “the largest genome in GATC Biotech’s history.”
There is no scientific publication yet of a human genome sequenced by next-generation technologies, but in May, 454 Life Sciences and Baylor College of Medicine announced that they sequenced the genome of Jim Watson using 454’s platform (see In Sequence 6/5/2007). Also, a team of Chinese researchers said this fall they sequenced the first Asian individual using Illumina’s Genome Analyzer (see In Sequence 9/25/2007).
Pohl acknowledged that the cost-effective production of high-quality human sequence data and the analysis of such large amounts of data will be challenging, but said he believes the company’s experience with next-generation technologies will give it an edge. “However, the final bioinformatics of a human genome, to whatever degree, will remain a challenge, until several human genomes have been resequenced.”
“We feel that we are, with our four leading sequencing technologies, equipped to go into producing human genome sequences.”
GATC has had requests for human sequencing services from two undisclosed academic research groups. One is a consortium of researchers that is currently applying for EU funding for a human sequencing project related to a specific disease area, the other one a German group that is “still at a very early stage,” according to Pohl. If these groups obtain their funding, GATC will provide them with sequencing services. Among them, these groups expect to sequence about 10 human genomes, he said.
But Pohl hopes interest in the service will not stop there. “We can also imagine that this is interesting for pharmacogenomics companies, for pharma companies, for diagnostics companies,” he said. So far, GATC has not had requests from industry, but it has high hopes for organizations like the International Serious Adverse Events Consortium, a collaboration of pharmaceutical companies, academic institutions, and the US Food and Drug Administration that plans to study genetic markers to predict serious drug-related adverse events.
In total, Pohl estimates, demand from all customer types will add up to “at least 100 genomes in the next three years.”
GATC is not the only service firm that is seeing demand for human genome sequencing. Clinical Data’s Cogenics division “receives requests for sequencing human genome segments and genomes of other similarly sized mammals,” Clive Higgins, Cogenics’ general manager for North America, told In Sequence by e-mail.
However, with its current capacity, it would take the company four years to complete a human genome at 20x coverage using 454’s sequencing technology, he said. “Demand will dictate adding additional technologies and capacities, e.g. Solexa, SOLiD, and Helicos,” he added. “The additional platforms would reduce the pricing and turnaround times.”
But bioinformatics might become the bottleneck, he cautioned. “Data analysis presents the primary limitation on the ability to assemble a complex genome and is the biggest challenge for sequencing the human genome.”
SeqWright, a service provider based in Houston, is also “seeing a demand for human genome sequencing services, especially when sequencing prices continue to drop,” SeqWright CEO Fei Lu told In Sequence by e-mail last week. She did not elaborate on how the company is responding to this demand.
Longer term, Pohl could also imagine offering the service directly to consumers. “We do see that one should take the first step before the second step,” he said, but “down the road, I think that will be the logical consequence.”
Other companies are currently gearing up to provide direct-to-consumer sequencing, including Knome, a Cambridge, Mass.-based startup (see In Sequence 10/30/2007).
Pohl cautioned, however, that at the moment, from a medical point of view, “there is probably not really the use to [have one’s genome sequenced] as a private person.”
If the new service catches on, GATC plans to expand both its staff and equipment. Pohl said he could imagine adding “a couple of dozen” new staffers, both in bioinformatics and in the wet lab, over the next two to three years, adding to a headcount of around 60 today.
In terms of adding more sequencing equipment, the company has no specific plans yet. “We would definitely have to acquire more sequencers,” Pohl said. “At the moment, we cannot really say which one would be the technology of choice, or how we would mix the different technologies. [This] is something we would find out after doing the first couple or half a dozen of the genomes.”