Complete Genomics, a start-up based in Mountain View, CA, has again lowered the stick in the financial limbo dance of human genome sequencing, announcing in the journal Science that it has sequenced three human genomes for an average cost of $4,400. The most recently sequenced genome–which happens to be that of genomics pioneer George Church–cost just $1,500 in chemicals, the cheapest published yet. A cost of about $1,000 is considered to be the price point at which average Americans might invest in having their genomes sequenced. The hope is that by making the process more affordable, genome analysis could become a routine part of medical care.
Complete Genomics first made waves in the sequencing scene in October 2008 when it announced plans to offer a $5,000 human genome sequencing service. The announcement generated both excitement and skepticism. Lowering the cost of sequencing would allow scientists to study large numbers of human genomes, which is now thought necessary to understand the genetic basis of complex disease. But the cheapest estimates at the time hovered around $50,000. Without details on specific costs, accuracy rates, and other metrics, many saw the Complete Genomics announcement as hype. (Others in the race to lower sequencing costs include San Diego-based Illumina, Cambridge, MA-based Helicos, and Applied Biosystems, based in Foster City, CA.)
Complete Genomics aimed to quell skepticism earlier this year by releasing proof-of-principle genome sequence data from a Caucasian male who is part of the International HapMap project, which has built a database of human genetic variation. Because some genetic information is already available for HapMap samples, sequencing the genomes of HapMap participants allows scientist to assess the accuracy of novel sequencing technologies. The new publication builds on that data, giving detailed cost estimates and describing the Complete Genomics technology. It’s also the first peer-reviewed article published by researchers at Complete Genomics.
In the paper, scientists describe the sequence of three human genomes: the previously released Caucasian male, a West African female who has also been sequenced through the HapMap project, and that of Church, a Harvard professor and head of the Personal Genome Project. Costs ranged from $8,005 for 87-fold coverage of one genome–because genomes are sequenced in fragments of DNA, they must be sequenced multiple times to correctly assemble those fragments–to $1,726 for 45-fold coverage of Church’s genome. The technology has an accuracy rate of about 99.999 percent, says Complete Genomics’ chief scientific officer, Radoje Drmanac, who adds that this is comparable to other methods.
“I think it compares nicely to the 1000 Genomes data sets we have been generating with Illumina data in terms of accuracy,” says Chad Nusbaum, co-director of the Genome Sequencing and Analysis program at the Broad Institute, in Cambridge, MA. (The 1000 Genomes project is an international effort to sequence human genomes from around the world.) Nusbaum’s team recently received data from five genomes sequenced by Complete Genomics, though it hasn’t had time to analyze the information. “If thedata resembles what they have in the paper, we will likely want to do more,” says Nusbaum.
Calculating the cost of sequencing a human genome is a tricky business–price estimates can vary depending on what’s included in the calculation. One common measure is the cost of the chemicals used, and this is what Complete Genomics used. However, this measure doesn’t incorporate the cost of the machines that do the sequencing, the human labor, or the computational effort required to assemble raw sequence information into a whole genome. “What’s important is not just the reagent costs, but also the cost of analyzing the sequence,” says Jeff Schloss, program director for technology development at the National Human Genome Research Center, in Bethesda, MD. “It’s unclear how computational costs for this method compare to some of the others.”