Complete Genomics has published data demonstrating the use of its long-fragment repeat (LFR) technology for whole-genome sequencing and haplotyping using just 10–20 human cells, or about 120 picograms of high molecular mass DNA. The technology, which the firm claims is at least 10-fold more accurate than any existing high-sensitivity method, enables full haplotype determination, or phasing, to sequence maternal and paternal chromosomes separately and thus identify whether two genetic variants within a single gene are both carried on the same or different homologous chromosomes. Complete Genomics maintains that in a future clinical setting, this will potentially enable more accurate disease diagnosis, provide insights into disease severity, and aid therapeutic decision making.
The technology, which uses barcodes to tag the individual DNA fragments, is described by the firm and its collaborators in Nature, in a paper titled “Accurate whole-genome sequencing and haplotying from 10–20 human cells”. Brock A. Peters, Ph.D., Radoje Drmanac, Ph.D., et al claim the reported studies demonstrate that the LFR platform can generate whole-genome sequences with just one error in 10 million base pairs (equivalent to about 600 in a whole human genome).
“By providing sequence data from both the maternal and paternal chromosomes independently, LFR is able to detect regions in the genome assembly in which only one allele has been covered,” the authors write. “Likewise, false positive calls are avoided because LFR independently, in separate aliquots, sequences both the maternal and paternal chromosomes 10–40 times.”
The team claims the ability to cost-effectively carry out diploid sequencing of a human genome starting from just a few cells will provide opportunities for comprehensively screening rare cell types, such as circulating tumor cells or preimplantation embryos generated through IVF.
While celebrating its technological achievements, this is not a happy time for the Complete Genomics business. The firm is currently defending two patent suits filed against it by Illumina, and having recorded a net loss of $20.2 million in the first three months of 2012 recently confirmed that it had engaged a financial specialist to look into possible ways forward, including a potential sale or merger of the company. Meanwhile, 55 jobs will be lost.
Reporting last month on the appointment of Jefferies & Company to help look at strategic options, Complete Genomics said it plans to focus on developing clinical applications for the whole human genome sequencing platform, while continuing to provide genome-sequencing services to research customers.