Genome sequencing provider Complete Genomics has announced a deal with the non-profit Inova Translational Medicine Institute, under which the company would sequence 1,500 complete human genomes to help explore the genetic basis of premature birth.
The Inova collaboration is one of many large-scale genome sequencing studies currently being planned and performed around the world. In some respects the study is actually quite a small one – only 250 “cases” (i.e. premature babies) are being sequenced, along with 250 normal-term control babies, which means the researchers will have low statistical power by the standards of modern genomics. However, sequencing this number of complete genomes to high depth is (as far as I know) unprecedented, and the inclusion of the parents of all of the children in the study will provide the team with the ability to do some very interesting analyses – for instance, looking at “de novo” mutations that arise in the babies but weren’t present in either parent, as well as exploring potential effects of the maternal genome. Maternal genetics are known to be important in determining the risk of premature birth: girls born prematurely have a higher risk of delivering a pre-term baby themselves (with twin studies suggesting between 15 and 40% of the risk is heritable), while paternal genes seem to have almost no effect.
This study certainly won’t definitively pin down the precise genetic causes of pre-term birth – that will require whole-genome sequencing in far larger numbers of samples – but should rather be seen as an important pilot project for wider-scale clinical implementation of whole-genome sequencing. Inova has larger ambitions in this arena: GenomeWeb reports that the institute is planning another study that would sequence the genomes of 2,000 babies who would then be followed prospectively, to see whether genome-scale information can provide useful in guiding healthcare.
Complete Genomics, like all other DNA sequencing companies, has always had the potentially enormous clinical sequencing market as their major long-term focus. In order to reach this market they will first need to get CLIA certification, which they say will happen by mid-2012, and – more importantly – to establish that their platform provides the accuracy and coverage required for serious clinical applications.
That second part will not be straightforward. Currently none of the major next-generation sequencing technologies (Complete’s in-house platform, Illumina’s HiSeq and MiSeq, Life Technologies’ SOLiD and Ion Torrent, Roche’s 454 and Pacific Biosciences’ RS) can provide clinical-grade accuracy for all of the potentially medically important regions of the genome. We can expect the already heated battle between these vendors (as well as not-yet-launched platforms like the Oxford Nanopore system) to intensify over the next twelve months as each of them attempts to position itself as “the sequencer you can trust” for clinical applications (including, but certainly not limited to, whole-genome sequencing). Ultimately each of these platforms will likely survive by finding their own specific niches, but which technology (or combination of technologies) will win out in the whole-genome space is currently entirely unclear.
However, the Inova deal is unquestionably a big win for Complete Genomics, which has been under assault by overall sequencing market leader Illumina ever since it launched its whole-genome sequencing service. Fifteen hundred genomes is a massive contract, no doubt won in the face of substantial competition from Illumina, and confirms Complete’s status as a serious contender for domination of the whole-genome market.
Anyway, while we wait to see who comes out on top of the sequencing race, those of us interested in genomic medicine have a daunting challenge ahead of us: figuring out how we can actually use the masses of information from new sequencing technologies to cost-effectively improve clinical care. Unfortunately this process will move far more slowly than the astonishing pace of change in the DNA sequencing arena – but projects like the Complete-Inova partnership will undoubtedly provide valuable lessons.