Quantum Leap In Newborn Whole Genome Sequencing

Mini nanopore genome sequencing device.

Mini nanopore genome sequencing device.


When a critically ill 3-month-old infant entered a Stanford hospital with unexplained seizures, physicians were mystified by the young patient’s illness. The infant displayed many signs of epilepsy, but brain scans found no abnormalities to indicate what could be causing the infant’s epileptic seizures.

Doctors quickly ordered an epilepsy gene panel to determine if the patient had common gene mutations associated with epilepsy. However, results could take weeks and there was a chance that the infant might have a rare disorder that would not be detected by a common gene panel.

Luckily, in the same hospital, Stanford researchers were busy creating an optimized method to detect and diagnose diseases— super rapid genome sequencing.

Genome sequencing is a process used to analyze a patient’s full DNA makeup. For physicians tasked with diagnosing rare genetic diseases, genome sequencing is an essential tool. It helps doctors determine if their patient’s genes are mutated and what genetic diseases they may have from those mutations.

In the past, it has taken weeks to months to receive DNA sequencing results. Now, Stanford scientists have found an improved method of genome sequencing that can diagnose a patient within the span of just eight hours.

How did they do this? The first step was to optimize the genome sequencing device. To do so, the Stanford team consulted Oxford Nanopore Technologies. Oxford Nanopore Technologies recently built a device containing 48 DNA sequencing units called flow cells. The device also contained an important feature called “long-read sequencing”.

Typically, DNA sequencing occurs by chopping a person’s genome into small DNA fragments. The fragments are then replicated and pieced back together using a standard human genome as reference. However, this approach does not always accurately capture the entirety of a patient’s genome. This means that it can be difficult, if not impossible, to locate mutations that occur over a large chunk of DNA. By using long-read sequencing which preserves much longer stretches of the patient’s genome, the chances of locating these long mutations and accurately diagnosing the patient are much higher.

Stanford’s theory was that by using long-read sequencing and all 48 flow units to simultaneously process a single patient’s genome, they could drastically reduce sequencing time, without compromising accuracy.

The nanopore device was successful—too successful. The device sequenced patient DNA at such high speeds that the lab’s computational system could not process the data. The Stanford team would have to amend their original approach or find some way to increase their computational power.

The team soon found that by funneling the data directly to a cloud-based storage system, they could increase computational power enough to process all the data produced by the nanopore device. Algorithms were then used to scan the sequenced DNA and look for mutations in the patient’s genome that could cause disease.

Using this super rapid genome sequencing technique, scientists scanned the 3-month-old patient’s full genome within just eight and a half hours. They found that the infant had a mutated CSNK2B gene. CSNK2B is a gene associated with a rare neurodevelopmental disorder called Poirier-Bienvenu which is characterized by early-onset epilepsy.

Within just a couple of days, doctors diagnosed the patient with Poirier-Bienvenu, prescribed the correct antiseizure medication, and provided the patient’s family with disease-specific counseling and a prognosis.

In contrast, the epilepsy gene panel results arrived 2 weeks later and were inconclusive.

This advance in genome sequencing marks a significant breakthrough in diagnostic tools. With the power to sequence a person’s full DNA within just hours, super rapid genome testing could become a widely available tool used to identify inheritable diseases in infants. By detecting these diseases at an early stage, families and doctors can avoid any further diagnostic testing, begin treatments as early as possible, and improve patient prognosis.

Rapid genome sequencing may also be the key to discovering and classifying mystery diseases in adult patients that are undiagnosed. Previous genetic tests relied on scanning a patient’s DNA for a pre-determined set of common genes. However, the algorithms used in super rapid genome testing can scan a patient’s full genome for all mutations suggested by scientific literature, even if the mutations were only discovered the day before.

Not only this but as genome testing continues to develop it may be a valuable tool against viruses like Covid-19 or the common cold. Much like the human body, viruses contain nucleic acids. These nucleic acids are either DNA or RNA, but both can be deciphered by genome sequencing. By using rapid genome sequencing, we can quickly identify viruses in a sick patient and offer the most effective medications against that specific virus. For pathogens as virulent and harmful as Covid-19, early identification and treatment through rapid genome testing may be the key to preventing wider spread.

This study marks significant progress towards personalized medicine. Now that scientists have discovered a method to make DNA sequencing more available, rapid genome sequencing could soon become a common tool found in every hospital and doctor’s office. As we continue to optimize our ability to sequence DNA, we can anticipate a critical shift towards personalized medical treatments that could increase patient care, improve overall health, and pave the way to new genetic discoveries.


Read the full article on Forbes.

© William A. Haseltine, PhD. All Rights Reserved.