In an industry first, a hand-held device sequences the entire human genome with 99.96% accuracy.
A milestone in genomic research was reached this week when scientists used a handheld Oxford Nanopore sequencer – the MinION – to assemble an entire human genome via direct long reads.
The scientists generated 91.2 Gb of sequence data, representing approximately 30x theoretical coverage. Over half the reads came in at more than 100 kb. “The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference,” the authors wrote. They reported that the accuracy of the assembly was more than 99.96% after incorporating complementary short-read sequencing data. Their paper was published in Nature Biotechnology.
Oxford Nanopore (ON) is a WuXi NextCODE technology partner, so this is exciting news for us and our customers as well. In October, 2017, we announced that our Shanghai sequencing laboratory would feature the first open-access installation of ON instruments in a laboratory in China.
We asked Dr. Hongye Sun, our Chief Technology Officer and head of our sequencing lab in Shanghai, about the significance of this latest news for our customers. “I think this is a breakthrough paper,” he says. “Until now, this technology has best proven its utility on smaller genomes [e.g. plants, bacteria or microbiomes], but we can now see several important uses for it in human genomics.”
Nanopore sequencing works by passing a strand of DNA through a nano-scale hole, or “nanopore,” while sending an ionic current at the same time. The DNA or RNA sequence is determined by measuring variations in the current as strands pass through the nanopore.
Unlike other sequencing techniques, this process does not require cutting genomes into millions of fragments only hundreds of bases long and preparing them with primers and reagents. Sun also notes “the robustness of electrical rather than optical signal capture.” As a result, these instruments can quickly and economically produce reads that are hundreds of thousands of bases long. That’s much longer than the standard sequencing process can handle.
In fact, until recently users were vying to be the first to use ON’s technology to achieve the first DNA read longer than 1 Mb. In December of 2017, a group of Australian scientists at the Kinghorn Centre for Clinical Genomics won that race using the technology to produce a 1.015 Mb read from Chromosome 19.
The authors of the more recent Nature Biotechnology paper, meanwhile, reported that the ON technology allowed them to close 12 gaps in the reference human genome, which is still technically incomplete. One of the challenges in completing the genome has been sequencing highly repetitive sequences. ON instruments’ ability to do longer reads elegantly addresses that problem.
This latest breakthrough enables at least three main applications for ON Nanopore technology in human genomics, according to Sun.
First, it can help researchers create a scaffold of long reads to complement short-read sequencing, which is the industry standard. The paper shows, he points out, that “Direct longer reads reveal structural variation and also seem to enable detection of methylation without PCR amplification.”
Second, this technology could be very useful for metagenomics, particularly for the integration of gut microbiome sequencing with germline sequencing in research, clinical and wellness applications.
Finally, Sun expects the MinION, in particular, could become a point-of-care instrument, thanks to its small size, ease of use, and cost, “which can give more people the opportunity to apply the technology.”
“This paper suggests the Nanopore technology can fill an important niche alongside standard short-read sequencing; more capital-intensive, traditional long-read sequencing; and technology that produces long reads from short-read data,” Sun says. “This is an extraordinarily exciting time to be in genomics and we feel privileged to be in the position to tap into all this cutting-edge technology to advance our and our partners’ products.”
We offer our congratulations to our partners at ON and look forward to applying these new capabilities in tandem with our range of partners in China and worldwide.