And in less than eight hours, they had diagnosed a child with a rare genetic disease, results that would take weeks of clinical laboratory testing, demonstrating the clinical value of the genomic process.
In another major advance in genetic sequencing, scientists at Stanford University School of Medicine have developed a method of rapidly sequencing the entire human genome of patients in as little as five hours. And the researchers used their discovery to diagnose rare genetic diseases in less than eight hours, according to a press release from Stanford Medicine. Their new “ultra-rapid genome sequencing approach” could lead to much faster diagnoses and improved clinical laboratory treatments for cancer and other diseases.
Stanford Medicine researchers have used nanopore sequencing and artificial intelligence (AI) technologies in a “mega-sequencing approach” that has redefined “fast” for genetic diagnostics. One study participant’s sequence – completed in just five hours and two minutes – set the first Guinness World Record for the fastest DNA sequencing to date, the press release said.
Stanford scientists have described their new method for rapid diagnosis of genetic diseases in the New England Journal of Medicine (NEJM) titled “Ultrafast Nanopore Genome Sequencing in a Critical Care Setting”.
“A few weeks is what most clinicians call ‘fast’ when it comes to sequencing a patient’s genome and returning results,” said a cardiovascular disease specialist. Euan Ashley, MD, Ph.D. (above), professor of medicine, genetics and biomedical data science, at Stanford University in the press release. “The right people suddenly came together to achieve something amazing. It really felt like we were approaching a new frontier. Their results could lead to faster diagnoses and clinical laboratory treatments. photo credit: Stanford Medicine.)
Need for rapid genetic diagnosis
In their NEJM article, Stanford scientists say prompt genetic diagnosis is critical to clinical management, improving prognosis and reducing critical care costs.
“While most critical care decisions need to be made within hours, traditional testing takes weeks and rapid testing takes days. We have discovered that nanopore genome sequencing can accurately and rapidly provide genetic diagnostics,” the authors wrote.
To complete their study, the researchers sequenced the genomes of 12 patients from two hospitals in Stanford, California. They used nanopore genome sequencing, cloud computing-based bioinformatics, and “personalized variant prioritization.”
Their findings included:
- Five people received a genetic diagnosis from the sequencing information in about eight hours.
- 42% diagnosis rate, about 12% higher than the average diagnosis rate for genetic disorders (researchers noted that not all conditions are genetically based and appropriate for sequencing).
- Five hours and two minutes to sequence a patient’s genome in one case.
- Seven hours and 18 minutes to sequence and diagnose this case.
How the Nanopore Process Works
To speed up the sequencing speed, the researchers used equipment from Oxford Nanopore Technologies with 48 sequencing units called “flow cells”, enough to sequence a person’s entire genome at once.
The Oxford Nanopore PromethION Flow Cell generates over 100 gigabases of data per hour, AI Time Journal reported. The team used a cloud-based storage system to enable computing power for real-time data analysis. The AI algorithms scanned the genetic code for errors and compared the patients’ genetic variants to the disease-associated variants found in the research data, Stanford explained.
According to an NVIDIA blog post, “Researchers accelerated both base calling and variant calling using NVIDIA GPUs on Google Cloud. Variant calling, the process of identifying million variants of a genome, has also been accelerated with NVIDIA Clara Parabricks, a computational genomics framework.
Rapid genetic test yields clinical benefits
“With our collaborators and some of the world’s genomics leaders, we have been able to develop a rapid sequencing analysis workflow that has already shown tangible clinical benefits,” said Mehrzad Samadi, PhD, Senior Engineering Manager at NVIDIA and co-author of NEJM paper, in the blog post. “These are the types of high-impact issues that we live to solve.”
In their paper, the Stanford researchers described their use of the rapid genetic test to diagnose and treat an infant who was suffering from seizures upon arrival at Stanford’s pediatric emergency department. In just eight hours, their diagnostic test revealed that the infant’s seizures were attributed to a mutation in the CSNK2B gene, “a variant and gene known to cause neurodevelopmental disorder with early onset epilepsy,” the researchers wrote.
“By accelerating every step of this process – from collecting a blood sample to sequencing the entire genome to identifying disease-linked variants –[the Stanford] It took the research team just hours to find a pathogenic variant and make a definitive diagnosis in a three-month-old infant with a rare genetic condition that causes seizures. A traditional gene panel analysis ordered at the same time took two weeks to show results,” AI Time Journal reported.
The Stanford research team wants to cut sequencing time in half. But for now, the rapid five-hour whole-genome sequence can be seen by clinical laboratory managers, pathologists and research scientists as a new gold standard in genetic sequencing for diagnostic purposes.
Stories like Stanford’s rapid diagnosis of a three-month-old patient with epileptic seizures underscore the ultimate value of advances in genomic sequencing technologies.
—Donna Marie Pocius
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