A team based at Stanford University has broken previous world records by sequencing a whole human genome in just five hours and two min using Oxford Nanopore’s PromethION 48 sequencer.
The record was achieved by Euan Ashley, a professor and clinician at Stanford University School of Medicine, and his team during a demonstration of how useful this type of fast sequencing can be for patients with genetic diseases.
In total, 12 unique samples from critical care patients with suspected genetic disease, but no clear diagnosis, had their genomes sequenced. Scientists from Oxford Nanopore Technologies, NVIDIA, and Google also contributed to the trial.
In addition to breaking sequencing records, the team also identified genetic variants that could be disease causing and had a genetic diagnosis in as little as 7 hours and 18 minutes for one patient.
As described in a letter published in the NEJM, the patients were enrolled at two hospitals in Stanford, California, between December 2020 and May 2021, and ranged in age from 3 months to 57 years.
Although the fastest run for sequencing and disease-causing variant identification was 7 hours 18 min, none of the analyses took longer than 20 hours and most were under 15 hours.
Overall, the experiment revealed pathogenic or likely pathogenic variants in five of the 12 samples, allowing treatments to start or change and allow rapid activation of clinical management plans for the patients and their families.
For example, one patient, a 3-month-old baby with epileptic symptoms had no brain abnormalities revealed on magnetic resonance imaging scanning. Eight hours and 25 minutes after being enrolled, a genetic variant in the CSNK2B gene was revealed. This gene variant has previously been linked with a neurodevelopmental disorder with early-onset epilepsy known as Poirier–Bienvenu neurodevelopmental syndrome.
A definitive diagnosis of this disorder was made. This stopped further diagnostic tests, allowed suitable family counselling and disease management planning to be put in place and helped clinicians pick the right epilepsy treatments for the infant.
The diagnostic odyssey for patients with genetic disease can take years, but patients who are critically ill do not have time for lengthy diagnostic tests. Decisions must be made quickly by clinicians and having the right clinical information to hand can be critical. Fast sequencing such as that demonstrated in this trial therefore has huge potential to improve medical care.
“Genomic information can provide rich insights and enable a clearer picture to be built. A workflow which could deliver this information in near real time has the potential to provide meaningful benefits in a variety of settings in which rapid access to information is critical,” said Gordon Sanghera, CEO, Oxford Nanopore Technologies.
“We designed PromethION to be able to prioritise time-to-result by using multiple flow cells together, just like cluster computing. We’re delighted to see the research team demonstrate the real-life potential of Nanopore technology through their research. I look forward to seeing the impact of real-time sequencing technology in the clinic one day.”