First Guinness World Record: Fastest Affordable DNA Sequencing Technology

The study was published in the New England Journal of Medicine

Fastest DNA sequencing technology could help undiagnosed patients find answers in just a few hours

Scientists at Stanford School of Medicine and their collaborators have developed a new ultra-fast genome-sequencing method for diagnosing rare genetic diseases in an average of eight hours, a feat almost unheard of in standard clinical care

"When sequencing a patient's genome and returning results, most clinicians call it 'rapid'," said Dr.

Genome sequencing allows scientists to see a patient's complete DNA makeup, which contains information on everything from eye color to genetic diseases

Now, a large-scale sequencing method devised by Ashley and his colleagues redefines the "rapidness" of genetic diagnosis: their fastest diagnosis was completed in just over seven hours

A paper describing the researchers' work was published Jan.

start making records

In less than six months, the team recruited and sequenced the genomes of 12 patients, five of whom had a genetic diagnosis from the sequencing information, in about a day's work in the office

In one case, a patient's genome was sequenced in just 5 hours and 2 minutes, setting the first Guinness World Record for the fastest DNA sequencing technology

Ashley said: "It's just an amazing moment where the right people suddenly come together and achieve amazing things

The time it took to diagnose this case was 7 hours and 18 minutes, which, according to Ashley, was about twice as fast as the previous record of the diagnosis based on genome sequencing (14 hours) maintained by the Rady Children's Institute

14 hours is still an impressively quick turnaround, Ashley said

Accelerate, accelerate, accelerate again

To achieve ultrafast sequencing speeds, researchers need new hardware

"We're not processing data fast enough," Ashley said

Graduate student Sneha Goenka has found a way to feed data directly into a cloud-based storage system, where computing power can be scaled up enough to sift through the data in real time

From start to finish, the team sought to speed up every aspect of patient genome sequencing

long read sequencing

Perhaps the most important feature of this diagnostic method, which can quickly find suspicious DNA fragments, is that it uses a method called long-read sequencing

"Mutations that occur on a large chunk of the genome are easier to detect by long-read sequencing

Only recently have companies and researchers honed the accuracy of long-read sequencing enough to be useful for diagnosis
.
That, combined with the once-high price tag, created an opportunity for Ashley's team
.
To his knowledge, this study is the first to demonstrate the feasibility of such long-read sequencing as a primary means of diagnostic medicine
.

For the study, Ashley's team provided accelerated genome sequencing technology to undiagnosed patients in the Stanford Hospital intensive care unit
.
They provided the patients under study with an established standard of care testing and employed an experimental approach to rapid genetic sequencing
.
Through these methods, they found answers to two important questions: Are the genes responsible for the patient's disease? If so, what specific DNA errors are causing the trouble?

Race against time to save the heart

Matthew Kunzman, Oregon
.
About a year ago, when Matthew was 13, an annoying cough and high fever sent him to the local doctor's office
.
"We thought it was the flu, or maybe Covid-19," said Matthew's mother, Jenny Kunzman
.
It turns out that coughing is the first sign of a heart disease called myocarditis
.
Myocarditis is inflammation of the heart that makes it difficult for the heart organ to pump blood to the rest of the body
.
Subsequent examinations at Matthew's local hospital revealed dire conditions: his heart was failing
.
His doctors advised his family to immediately fly to Stanford Hospital for treatment
.

Hours later, Matthew and his father, Matthew Kunzman Sr.
, were taken to Stanford Hospital
.
Jenny Kunzman arrived at the hospital a day later to find her son's condition had worsened
.

There are two reasons why an essentially healthy 13-year-old might experience this type of heart failure, Ashley said
.
One, called myocarditis, occurs when immune cells swarm the heart, usually triggered by a virus or other physical stress
.
The other is a genetic cause, a genetic mutation associated with heart function
.

Knowing the difference is crucial, Ashley said
.
"Myocarditis is usually reversible," he said
.
"With treatment, the heart can return to normal
.
But the genetic condition is not
.
If Matthew's condition is genetic, the only solution may be a heart transplant
.
"

Gorzynski approached Matthew's parents, explained the rapid sequencing study, and asked if they would like to include the boy in the study
.
Jenny Kunzman said: "They told us they were doing a whole new study to try to speed up the diagnosis process
.
They asked if we would like to participate, and we said, 'Of course we do
.
' We wanted to get as much information as possible, Trying to find out why
.
"

Using a few milliliters of Matthew's blood, the team began the process of rapid genetic sequencing
.
"Over the course of a few hours, the sequencing data showed that this was genetic," Ashley said
.

With this information, Matthew was immediately placed on the heart transplant list
.
21 days later, he got a new heart; today, about a year later, his mum says he's recovering "extremely well"
.

suspected epilepsy

In another case, a 3-month-old patient presented to the Stanford Pediatric Emergency Department with an unexplained seizure
.
It was clear that the baby had some form of epilepsy, but what was causing the symptoms was unclear
.

The researchers sequenced the genomes of patients, running the data through mutation detection algorithms and cross-referencing public genomic and disease data
.
They also called for standard clinical diagnostic testing for blood biomarkers associated with seizures of genetic origin
.
Just over eight hours later, thanks to rapid sequencing data, the team had an answer: The young patient's tics were caused by a mutation in a gene called CSNK2B
.

If the team had relied only on standard tests, no diagnosis would have been made at the time, though further tests might eventually reveal the correct diagnosis in patients, Ashley said
.
"We're going to spend many weeks in the dark," he said
.

Standard tests check patients' blood for markers associated with disease, but they scan for only a few well-documented genes
.
Commercial labs routinely perform these tests, but are slow to update the molecules they screen, meaning newly discovered disease-causing mutations can take a long time to be integrated into tests
.
This can lead to misdiagnosis
.

That's why rapid genome sequencing could be a game-changer for patients with rare genetic diseases, Ashley said
.
Scientists can scan a patient's entire genome for any and all genetic variants mentioned in the scientific literature, even if that gene was discovered the day before
.
In addition, if the patient does not receive a genetic diagnosis in the first place, scientists still have hope of finding new genetic variants associated with the patient's disease
.

Interest from other clinicians has already started pouring in
.
"I know people at Stanford who are excited to hear that we can have a genetic diagnosis in a few hours," Ashley said
.
"Genetic testing is not considered a quick recovery test
.
But we are changing that perception
.
"

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