Increasing the sequencing coverage of the DNA makes it possible to call bases for 96 to 97 percent of the genome with very high confidence. However, there are certain regions of the genome that are difficult to sequence, Drmanac said, and within the majority that can be sequenced there are still about 4,200 errors. However, by eliminating the 5 percent of calls that have lower confidence, the error rate for the remaining calls is just 366 per genome, or 1 for every 7 megabases. “We can get to clinical quality, even with our standard process,” he said, “and we have other processes that will further improve [quality].”
Complete Genomics expects to be able to sequence 2,000 genomes per month by the end of 2012, up from 800 at the time of the workshop. Better instruments could boost that rate to 100,000 genomes per year, and the company has the goal of being able to do millions of genomes per year. “That’s coming,” Drmanac said. “We don’t need to wait for new inventions. It’s just regular improvements.”
The company has a diverse base of more than 100 users, including organizations from government, industry, academia, and private industry. These organizations have been using the technology to investigate cancer, de novo mutations, genomic variation and disease, and the potential of translational medicine. “It’s a golden age where we can sequence millions of genomes in cancers, in unknown disease, and in frequent disease,” Drmanac said. “It can be done in the next 5 to 6 years.”
Drmanac proposed the idea of a million-genome project, or perhaps a 10-million-genome project, to understand both health and disease. “Hopefully we can reduce cost at the same time,” he added. “It’s very difficult and not guaranteed, but I think with the genome we hopefully can do that.”
Sequencing capabilities will continue to grow exponentially, both in terms of capacity and accuracy. In a few years, 1,000 times coverage may be routine. A genome sequence could be done at birth—or even preimplantation—to provide a foundation for health care and research throughout life. Understanding of biological function is exploding, and sophisticated software to interpret genomes is undergoing rapid development. Given this rapid growth in understanding and capability, perhaps all people enrolled in clinical trials should have their genomes sequenced to minimize risks and maximize efficiency, Drmanac suggested. Genomic data will need to be integrated with complete transcriptome and epigenome analysis for the relevant tissues of each subject, but whole genome sequencing can provide a foundation to integrate over other kinds of data. In this way, drugs could be developed for distinct genomic states and individual DNA sequences, such as genetically engineered stem cells or drugs that attack only cancer cells with specific DNA signatures.