Nearly 100,000 patients submitted saliva samples to a genetic testing laboratory, providing insights into their disease risk
Researchers at Mayo Clinic have employed next-generation sequencing technology to produce a massive collection of exome data from more than 100,000 patients, offering a detailed look at genetic variants that predispose people to certain diseases. The study, known as Tapestry, was administered by doctors and scientists from the clinic’s Center for Individualized Medicine and produced the “largest-ever collection of exome data, which include genes that code for proteins—key to understanding health and disease,” according to a Mayo Clinic news release.
For our clinical laboratory professionals, this shows the keen interest that a substantial portion of the population has in using their personal genetic data to help physicians identify their risk for many diseases and types of cancer. This support by healthcare consumers is a sign that labs should be devoting attention and resources to providing these types of gene sequencing services.
As Mayo explained in the news release, the exome includes nearly 20,000 genes that code for proteins. The researchers used the dataset to analyze genes associated with higher risk of heart disease and stroke along with several types of cancer. They noted that the data, which is now available to other researchers, will likely provide insights into other diseases as well, the news release notes.
“What we’ve accomplished with the Tapestry study is a blueprint for future endeavors in medical science,” said gastroenterologist and lead researcher Konstantinos Lazaridis, MD (above), in the news story. “It demonstrates that through innovation, determination and collaboration, we can deeply advance our understanding of DNA function and eventually other bio-molecules like RNA, proteins and metabolites, turning them into novel diagnostic tools to improve health, prevent illness, and even treat disease.” Some of these newly identified genetic markers may be incorporated into new clinical laboratory assays. (Photo copyright: Mayo Clinic.)
How Mayo Conducted the Tapestry Study
One notable aspect of the study was its methodology. The study launched in July 2020 during the COVID-19 pandemic. Since many patients were quarantined, researchers conducted the study remotely, without the need for the patients to visit a Mayo facility. It ran for five years through May 31, 2024. The news release notes that it’s the largest decentralized clinical trial ever conducted by the Mayo Clinic.
The researchers identified 1.3 million patients from the main Mayo Clinic campuses in Minnesota, Arizona, and Florida who met the following eligibility criteria:
Participants had to be 18 or older,
they had to have internet and email access, and
be sufficiently proficient in speaking and reading English.
More than 114,000 patients consented to participate, but some later withdrew, resulting in a final sample of 98,222 individuals. Approximately two-thirds were women. Mean age was 57 (61.9 for men and 54.3 for women).
“It was a tremendous effort,” said Mayo Clinic gastroenterologist and lead researcher Konstantinos Lazaridis, MD, in the news release. “The engagement of such a number of participants in a relatively short time and during a pandemic showcased the trust and the dedication not only of our team but also of our patients.”
He added that the researchers “learned valuable lessons about some patients’ decisions not to participate in Tapestry, which will be the focus of future publications.”
Three Specific Genes
Enrolled patients were invited to visit a website, where they could view a video and submit an eligibility form. Once approved, they completed a digital consent agreement and received a saliva collection kit. Participants were also invited to provide information about their family history.
Helix, a clinical laboratory company headquartered in San Mateo, Calif., performed the exome sequencing.
Though Helix performed whole exome sequencing, the researchers were most interested in three specific sets of genes:
Patients received clinical results directly from Helix along with information about their ancestry. Clinical results were also transmitted to Mayo Clinic for inclusion in patients’ electronic health records (EHRs).
Among the participants, approximately 1,800 (1.9%) had what the researchers described as “actionable pathogenic or likely pathogenic variants.” About half of these were BRCA1/2.
These patients were invited to speak with a genetic counselor and encouraged to undergo additional testing to confirm the variants.
Tapestry Genomic Registry
In addition to the impact on the participants, Mayo Clinic’s now has an enormous amount of raw sequencing data stored in the Tapestry Genomic Registry, where it will be available for future research.
The database “has become a valuable resource for Mayo’s scientific community, with 118 research requests submitted,” the researchers wrote in the news release. Mayo has distribution more than a million exome datasets to other genetic researchers.
“What we’ve accomplished with the Tapestry study is a blueprint for future endeavors in medical science,” Lazaridis noted. “It demonstrates that through innovation, determination, and collaboration, we can deeply advance our understanding of DNA function and eventually other bio-molecules like RNA, proteins and metabolites, turning them into novel diagnostic tools to improve health, prevent illness, and even treat disease.”
Everything about this project is consistent with precision medicine, and the number of individuals discovered to have risk of cancers is relevant. Clinical laboratory professionals understand these ratios and the importance of early detection and early intervention.
List also includes precision oncology, liquid biopsies, and early diagnosis of pancreatic cancer
Pathologists and clinical laboratory managers will be interested to learn that in a recently updated article the World Economic Forum (WEF) identified a dozen important recent breakthroughs in the ongoing fight to defeat cancer, including some related to pathology and clinical laboratory diagnostics.
The article noted that approximately 10 million people die each year from cancer. “Death rates from cancer were falling before the pandemic,” the authors wrote. “But COVID-19 caused a big backlog in diagnosis and treatment.”
The Swiss-based non-profit is best known for its annual meeting of corporate and government leaders in Davos, Switzerland. Healthcare is one of 10 WEF “centers” focusing on specific global issues.
Here are four advances identified by WEF that should be of particular interest to clinical laboratory leaders. The remaining advances will be covered in part two of this ebrief on Wednesday.
“Our study represents a major leap in cancer screening, combining the precision of protein-based biomarkers with the efficiency of sex-specific analysis,” said Novelna founder and CEO Ashkan Afshin, MD, ScD (above), in a company press release. “We’re not only looking at a more effective way of detecting cancer early but also at a cost-effective solution that can be implemented on a large scale.” The 12 breakthroughs listed in the World Economic Forum’s updated article will likely lead to new clinical laboratory screening tests for multiple types of cancer. (Photo copyright: Novelna.)
Novelna’s Early-Stage Cancer Test
Novelna, a biotech startup in Palo Alto, Calif., says it has developed a clinical laboratory blood test that can detect 18 early-stage cancers, including brain, breast, cervical, colorectal, lung, pancreatic, and uterine cancers, according to a press release.
In a small “proof of concept” study, scientists at the company reported that the test identified 93% of stage 1 cancers among men with 99% specificity and 90% sensitivity. Among women, the test identified 84% of stage 1 cancers with 85% sensitivity and 99% specificity.
The researchers collected plasma samples from 440 individuals diagnosed with cancers and measured more than 3,000 proteins. They identified 10 proteins in men and 10 in women that correlated highly with early-stage cancers.
“By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate,” states a BMJ Oncology press release.
The company says the test can be manufactured for less than $100.
“While further validation in larger population cohorts is necessary, we anticipate that our test will pave the way for more efficient, accurate, and accessible cancer screening,” said Novelna founder and CEO Ashkan Afshin, MD, ScD, in the company press release.
Precision Oncology
According to the National Institutes of Health’s “Promise of Precision Medicine” web page, “Researchers are now identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that develop in totally different parts of the body can sometimes, on a molecular level, have a lot in common. From this new perspective emerges an exciting era in cancer research called precision oncology, in which doctors are choosing treatments based on the DNA signature of an individual patient’s tumor.”
“These advanced sequencing technologies not only extend lifespans and improve cure rates for cancer patients through application to early screening; in the field of cancer diagnosis and monitoring they can also assist in the formulation of personalized clinical diagnostics and treatment plans, as well as allow doctors to accurately relocate the follow-up development of cancer patients after the primary treatment,” Wang wrote.
Based in China, Genetron Health describes itself as a “leading precision oncology platform company” with products and services related to cancer screening, diagnosis, and monitoring.
Liquid and Synthetic Biopsies
Liquid biopsies, in which blood or urine samples are analyzed for presence of biomarkers, provide an “easier and less invasive” alternative to conventional surgical biopsies for cancer diagnosis, the WEF article notes.
These tests allow clinicians to “pin down the disease subtype, identify the appropriate treatment and closely track patient response, adjusting course, if necessary, as each case requires—precision medicine in action,” wrote Merck Group CEO Belén Garijo, MD, in an earlier WEF commentary.
The WEF article also highlighted “synthetic biopsy” technology developed by Earli, Inc., a company based in Redwood City, Calif.
As explained in a Wired story, “Earli’s approach essentially forces the cancer to reveal itself. Bioengineered DNA is injected into the body. When it enters cancer cells, it forces them to produce a synthetic biomarker not normally found in humans.”
The biomarker can be detected in blood or breath tests, Wired noted. A radioactive tracer is used to determine the cancer’s location in the body.
“Pancreatic cancer is one of the deadliest cancers,” the WEF article notes. “It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years.”
The test is based on a technology known as high-conductance dielectrophoresis (DEP), according to a UC San Diego press release. “It detects extracellular vesicles (EVs), which contain tumor proteins that are released into circulation by cancer cells as part of a poorly understood intercellular communication network,” the press release states. “Artificial intelligence-enabled protein marker analysis is then used to predict the likelihood of malignancy.”
The test detected 95.5% of stage 1 pancreatic cancers, 74.4% of stage 1 ovarian cancers, and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas, they wrote.
“These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests,” said co-senior author Scott M. Lippman, MD.
Look to Dark Daily’s ebrief on Wednesday for the remainder of breakthroughs the World Economic Forum identifies as top advancements in the fight to defeat cancer.
One of the world’s fastest growing medical laboratory companies in India is using digital pathology systems and AI to replace older diagnostic technologies
Artificial intelligence (AI) is gaining acceptance around the world and use of AI to analyze digital pathology images is expected to be a major disruptor to the profession of anatomic pathology. Internationally, several pathology companies already use AI-powered solutions to diagnose cancer.
One such example is Neuberg Diagnostics, a fast-growing clinical laboratory company in Chennai, India. Neuberg has been using AI to review digital pathology images for several years, according to Chairman and Managing Director GSK Velu, PhD, BPharm.
“We already use AI in our laboratories,” Velu said in an exclusive interview with Dark Daily. “Our main reference laboratories currently use digital pathology systems to support the pathologists and many of them are using AI with these digital pathology systems.
“AI and data analytics tools are being used in other departments too, such as in our wellness department where we use AI for predictive analytics,” he added. “We also use AI in our genomics division, and we are introducing AI into other divisions slowly and steadily.”
Neuberg operates 120 laboratories in an extensive network in India, South Africa, and the United Arab Emirates (UAE), and now in the US as well.
“Our idea is to enhance the access and affordability for next-generation techniques, meaning molecular diagnostics, genomics, pathology, digital pathology, proteomics, metabolomics, and all that. This is the spirit behind Neuberg Diagnostics,” said GSK Velu, PhD, BPharm (above), Chairman and Managing Director of Neuberg Diagnostics, in an exclusive interview with The Dark Report. Clinical laboratories that are considering investing in digital pathology technologies may want to follow its development at Neuberg’s Centre for Genomic Medicine in Raleigh, NC, which opened in May. (Photo copyright: Neuberg Diagnostics.)
Replacing Older Pathology Technologies
As has been happening at other anatomic pathology centers around the world, Neuberg has been using digital pathology systems to replace older technologies. “One of our largest labs is our Bangalore Reference Lab,” Velu said. “There, we do not use microscopes for histopathology, and that lab has used digital pathology for routine review of specimens for several years now.
“But because artificial intelligence is still emerging, we can’t rely on AI with all of our digital pathology systems,” he added. “Although, of course, AI is certainly an aid to everything we do with digital pathology.
“For a variety of reasons, the adaptation of artificial intelligence in anatomic pathology is not happening as effectively nor as fast as we would like,” he noted. “So, for now, we need to wait and watch a bit longer, either because adaptation by pathologists is slow, or because AI tools are still a bit of a worry for some pathologists.
Younger Pathologists Adapt Faster to Digital Pathology
One reason could be that conventional pathologists worry about relying completely on AI for any diagnosis, Velu noted. “I’m certain that the more recent generation of pathologists who are now in their 30s, and the new people coming into pathology, will start adapting more quickly to digital pathology and to AI faster than the older generation of pathologists have done.
“The younger pathologists have a greater appreciation for the potential of digital pathology, while the older pathologists don’t want to let go of conventional diagnosis methods,” he added.
“For example, we have not yet seen where pathologists are reviewing breast image scans,” he commented. “But, at the same time, AI has been well-accepted among radiologists who are reviewing breast mammography scans.”
In India and in other markets worldwide, radiologists have adapted AI tools for breast mammography scans to diagnose breast cancer, he noted. “But that’s not happening even among pathologists who are doing cancer screening,” he said.
Velu suggested that another reason for the slow adoption of AI tools in pathology is that these systems are relatively new to the market. “Maybe the AI tools that are used with digital pathology are not as reliable as we hoped they would be, or they are not fully robust at the moment,” he speculated. “That’s why I say it will take some time before the use of AI for diagnosis becomes more widespread among pathologists. So, for now, we must wait until digital pathology and AI tools work together more seamlessly.
Replacing Conventional Pathology Technologies and Methods
“When those two technologies—AI and digital pathology systems—are linked more closely, their use will take hold in a substantial way,” Velu predicted. “When that happens, they are likely to replace conventional pathology methods completely.
“Currently, we are in the early stages of a transformation,” he added. “In our labs, you can see that the transformation is ongoing. We are using digital pathology systems even in our smaller labs. Then, the staff in our smaller labs do the processing of slides to convert them to digital images and send them to our labs in the larger cities. There, the professional staff uses AI to review those digital images and issue reports based on those images.
“Using our digital pathology systems and AI in that way means that we can make that technology available even in smaller towns and villages that have access only to our smaller labs,” he commented.
Velu added that wider use of digital pathology systems could improve the quality of care that pathologists deliver to patients in a significant way, particularly in rural areas. “Here in India, we are not seeing a huge shortage of pathologists, except in rural areas and villages,” he explained. “In those places, we could run short of pathologists.
“That is the reason we are trying to adapt the use of telepathology more widely,” he noted. “To do that, we might have technicians and histologists who will do just processing of slides so that they can send the digital images to our pathologists located in larger cities. Then, those surgical pathologists will review the cases and send the reports out. That’s the model that we are trying to slowly follow here.”
As use of digital pathology images increased, many predicted that specimens would flow from the US to India. This would happen because of the belief that the lower cost of surgical pathology in India would successfully draw business away from pathology groups here in the United States.
However, Neuberg turned the tables on that belief when it announced the opening of its Neuberg Centre for Genomic Medicine (NCGM), a state-of-the-art esoteric and genetic testing laboratory in Raleigh, NC. The NCGM lab is CLIA-certified and Neuberg says it is ready to compete with labs in this country on their home turf.
These are reasons why pathologists and pathology practice administrators in the United States may want to watch how Neuberg Diagnostics continues to develop its use of digital pathology platforms and AI-powered digital image analysis tools throughout its international network of laboratories.
