By Julia Karow
Users and vendors of second-generation sequencing technologies — including those from Illumina, Applied Biosystems, and Helicos BioSciences — have made various claims over the last few months about how much — or how little — it costs to sequence a human genome on their respective platform.
But even for a single platform, there seems to be no consent on the current cost of sequencing a human genome. Several users of the Illumina Genome Analyzer — arguably the platform used for most human genome sequencing today — interviewed by In Sequence offered different cost estimates, ranging from less than $40,000 to more than $200,000 per genome. Opinions also differed on what should or should not be included in that cost.
Meanwhile, Illumina itself is offering human genome sequencing at different price points. This spring, the company started a $48,000 personal genome sequencing service, targeted at consumers, that sequences individuals’ genomes to 30-fold depth (see In Sequence 6/16/2009). The company delivered its first completed genome under this service in July (see In Sequence 9/1/2009).
At the same time, Illumina has been quoting research customers prices of approximately $140,000 per human genome as recently as last month, according to several sources who requested anonymity to preserve their relations with the vendor.
An Illumina spokesperson told In Sequence this week that Illumina recently lowered its price for research customers but did not provide specifics on the new pricing before press time. She said that Illumina aimed for a price under $50,000 for the consumer market in order to be attractive to individuals and to prepare for when the market will grow. Illumina CEO and President Jay Flatley said in a company statement at the time of the service launch that “by providing this service now, Illumina can help catalyze the development of the infrastructure and physician education that will be necessary as genomic information becomes medically more meaningful.”
According to Stephen Kingsmore, president and CEO of the National Center for Genome Resources, “the price is going to depend on the quality of the finished product.” NCGR, based in Santa Fe, NM, is a non-for-profit research center with eight GAII instruments and is an Illumina-certified service provider.
Kingsmore put the price tag at $250,000 for “a well-annotated genome, with a lot of technical analysis to make sure that everything is kosher because there are many, many ways to get misled” by artifacts.
He did not elaborate on what exactly goes into this price, but said that the problem is that “there is no clear definition of when you are finished with a human sequence.” For example, if the goal is to reach a coverage of, say, 30-fold, there is still the question of whether to use short-insert or long-insert libraries, the latter being “a lot more expensive.”
In addition, depending on the nature and the amount of analysis required, the cost is likely going to be significantly higher than $250,000, he said. This year, NCGR sequenced three human genomes, one of which — the genome of a Korean individual, sequenced in collaboration with researchers at Seoul National University — was published in Nature this spring (see In Sequence 6/14/2009).
That genome cost “probably more like three quarters of a million dollars,” a large portion of it analysis costs, he said. Apart from compute costs, “an awful lot of manual analysis” is required. “It’s a very large amount of human effort.”
Sequencing consumables for that project totaled about $200,000, according to the Korean team.
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Manual annotation might decrease the analysis costs in the future, Kingsmore reckoned, once researchers agree on a common set of standards for human genome sequencing. “As soon as that happens, you can code up an automated solution, and then it’s just the cost of running that set of algorithms. That would bring the cost down quite a lot. But right now, it’s still an art, and a lot of custom scripts and a lot of manual interpretation of output.”
The cost of analysis is also determined by a researcher’s objectives, he said. “It may be that somebody is only interested, in, say, Mendelian traits, or maybe in a particular illness spectrum, or it may be that it’s really an evolutionary question,” each defining the type of analysis needed.
Marcus Benz, chief operating officer of commercial sequencing service provider GATC Biotech of Constance, Germany, said that a rough calculation that includes consumables, machine, maintenance, and labor costs and uses Illumina list prices puts the cost of sequencing a human genome on a single instrument at currently more than €100,000, or about $150,000, not including downstream bioinformatics analysis.
The price is based on a 30-fold coverage of a human genome with 76-base paired-end reads and a single short-insert library, although Benz stressed that this might not be sufficient, depending on what customers are aiming to achieve with their project. Actual project costs may vary if a lower or higher coverage is sought, or if different insert size libraries are required, according to Benz. “If you want to do a genome, the quality depends on what you want to do with it later on,” he said.
Assuming that each run generates 16 gigabases of data, almost six runs are required per genome, costing almost €50,000 in consumables, he said. Adding to that are approximately €50,000 to €60,000 per genome in fixed costs, consisting of instrument depreciation, maintenance, and personnel, but not overhead, other lab material needed, storage, or in-depth bioinformatic analysis. Also not included are R&D costs to improve lab protocols or write new scripts.
Bioinformatics analysis could add another €10,000 to €60,000 per genome, he said, both in equipment costs for computers and in personnel, given that a bioinformaticist can easily spend two months on analyzing a single genome, depending on the project goal.
GATC Biotech is well aware that it will not be able to match Illumina's own prices. “You never can beat the price of your own vendor if they offer the same service,” Benz said. However, unlike Illumina, the company offers services on several sequencing platforms.
The company, which recently announced plans to expand (see other article in this issue) currently has two Genome Analyzers installed, in addition to two 454 GS FLX machines and seven ABI 3730s, and like NCGR, is a certified Illumina service provider.
Some academic groups are coming up with lower costs for producing a human genome sequence. The Genomic Analysis Facility of the Duke Institute for Genome Sciences and Policy, for example, which has 11 Genome Analyzers installed, obtains more than 25 gigabases of high-quality data per run now, and expects to reach 40 gigabases in the next month or so. According to Kevin Shianna, the facility's director, his cost of producing and QC-ing the sequence of a human genome today is less than $40,000, including consumables, labor, and instrument costs, and he expects this price to fall to $10,000 early next year.
Temporary storage costs are not included, although that is a “huge up-front cost,” he said. The institute has spent “well over” $500,000 for data storage and computational upgrades, but “if this is split over the 400 to 500 genomes we plan to sequence over the next two years, then maybe it adds $1,000 per genome.” He did not mention the cost of in-depth data analysis.