A team from Stanford Medicine has set a Guinness World Record for the fastest time to sequence a whole genome. The developed technique is able to provide a genetic diagnosis in under eight hours, a timescale previously unheard of. The new method has the potential to transform how we diagnose critically ill patients.
The need for speed
When a patient is critically ill, it is important that crucial decisions regarding their care are made within hours. For individuals with genetic diseases, genome sequencing is vital for diagnosing and therefore treating them. However, even the most rapid of genetic testing currently takes days, and traditional testing requires weeks. This wastes precious time in which patients could already be receiving care for their condition. Therefore, a team from Stanford Medicine set out to develop a method that could provide genetic diagnoses at a fraction of the normal time. Their results and methodology are outlined in a letter published in the New England Journal of Medicine.
The researchers developed a sequencing workflow using nanopore technology, which carries out long-read whole genome sequencing. They enrolled 12 patients from hospitals in California. The study obtained a genetic diagnosis in five of these patients.
“Mutations that occur over a large chunk of the genome are easier to detect using long-read sequencing. There are variants that would be almost impossible to detect without some kind of long-read approach,” senior author Euan Ashley said. Long-read sequencing is also much faster: “That was one of the big reasons we went for this approach.”
The company Oxford Nanopore Technologies developed new hardware especially for this project. They built a machine containing 48 sequencing units, known as flow cells. Each cell was used simultaneously to sequence one person’s genome, which allowed for incredibly fast sequencing.
In fact, the sequencing data was produced so fast that it could not be processed quickly enough with existing software systems. Therefore, the team developed an updated bioinformatics framework with the ability to transfer and align raw sequencing data in just 34 minutes. In comparison, the previous fastest time was seven hours and 21 minutes. Specialised algorithms were also utilised to search the sequences for potential disease-causing mutations.
The Stanford team were able to shorten sequencing times so much that they broke multiple records. Amazingly, the Guinness World Record for the fastest DNA sequencing of a genome was set with a time of just five hours and two minutes.
The scientists also broke the record for making the fastest genetic diagnosis. The time taken from the arrival of a patient’s blood sample in the lab to initial diagnosis took just seven hours and 18 minutes. This was almost twice as fast as the previous record of around 14 hours.
The diagnoses suggested by the technology were not just fast, but accurate. The results were immediately reviewed by medical doctors to ensure that the diagnosis matched the symptoms patients were presenting. In one patient, a three-month old with unexplained seizures, the team’s new sequencing methodology was able to successfully identify a genetic cause – in just eight hours and 25 minutes. This allowed the infant to immediately receive targeted treatment and bypassed the need for potentially weeks of testing to find the underlying cause.
Fast diagnosis has huge implications for patients. It allows them to receive precision care weeks earlier than they would have done had they undergone current genetic testing.
However, this record-breaking DNA sequencing method does not come cheap. The costs range from around $5,000 to $7,300 per sample. The scientists hope that medical insurers in the US will soon cover genetic sequencing to allow more patients to access this life-saving technology.
For the time being, the researchers plan to offer rapid diagnosis to patients in ICU wards at Stanford Hospital and Lucile Packard Children’s Hospital Stanford. They hope that in the future, the technology can be implemented in other hospitals too. The team also plans to cut testing times even further.
“I think we can halve it again,” Ashley said. “If we’re able to do that, we’re talking about being able to get an answer before the end of a hospital ward round. That’s a dramatic jump.”
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