Investigators at and a consortium of international scientists have sequenced the three billion bases of DNA in the human genome using an inexpensive, portable device. Reaching the milestone puts genome sequencing at scientists' fingertips, opening the technology to a myriad of possible uses.
With this technology, doctors could monitor cancer progression at a patient's bedside. Investigators could carry out rapid forensic analysis at the scene of a crime. Epidemiologists could diagnose puzzling diseases in the field. All with a device that fits in the palm of your hand.
"The technology is ready for prime time with respect to its accuracy and ability to read long, complex DNA sequence," says the study's co-author associate professor of Human Genetics at U of U Health and associate director of the . He and his graduate student, the study's co-first author Thomas Sasani, demonstrated that the tiny device is superior over current standards at characterizing large, structural changes in the human genome that can cause disease. The research was published online in .
The advance was made possible by improvements to nanopore sequencing, a technology developed by Oxford Nanopore Technologies that is fundamentally different from today's standard platforms. At a cost of about $1,000, the MinION is orders of magnitudes cheaper than existing sequencing devices.
Another advantage is the unique way by which the device sequences DNA. Current technologies require that the genetic material be chopped into small sections before it is read. Then the sequence is assembled back together like pieces of a puzzle, a process that can introduce error.
With nanopore, genetic material is threaded through small holes in the device, and electrical sensors read the long tickertape of DNA base pairs as they pass by. The study reports ultra-long reads of up to 882,000 bases – over 1,000 times longer than is possible with standard technology—and future methodological advances should make even longer stretches possible.
With this capability, the scientists were able to analyze regions of the human genome that, until now, had remained difficult to decipher. MinION can tackle extensive spans of repetitive sequence such as those found in telomeres, structures on the ends of the chromosomes that carry our genes. Being able to analyze telomere repeats more accurately could yield new insights into aging.
The same principles could be applied to carefully investigate structurally complex sequences known to be involved in clinical conditions such as Huntington's disease.
"When scientists had reported in 2003 that they had sequenced the human genome it was kind of a lie," says Quinlan. There were still small sections of DNA that had remained unreadable. This study has created the most complete human genome assembled with a single technology.
The most significant aspect of the work, says Sasani, is that it benchmarks MinION's performance. If the tiny technology can motor through the long and complex human genome, it should be able to sequence nearly anything. "Nanopore can do things that no other technology can," he says. Scientists are still working to speed analysis but the capability is there.
"What's incredibly exciting to me is that this technology is moving at an incredible pace," says Quinlan. MinION was released to first generation users in 2014. Already scientists are using MinION to identify new species by sequencing genomes of animals in the wild, and monitoring water and other environmental samples for contamination. Now, MinION will be able to help scientists interpret previously unexplored genetic contributors to disease.
"Despite their relevance to disease, we currently have great difficulty interrogating structurally complex parts of the human genome. MinION is changing that," says Quinlan. "I'm eager to see what will be possible in another four years."
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The study is published as "Nanopore sequencing and assembly of a human genome with ultra-long reads" in Nature Biotechnology.
The research was led by investigators at University of Birmingham and University of Nottingham in collaboration with scientists at U of U Health; University of California, Santa Cruz; National Human Genome Research Institute; University of British Columbia; University of East Anglia; Ontario Institute for Cancer Research; and University of Toronto. Quinlan and Sasani were funded by the National Institutes of Health.