Expanded genomic dataset includes a wider racial diversity which may lead to improved diagnostics and clinical laboratory tests
Human genomic research has taken another important step forward. The National Institutes of Health’s All of Us research program has reached a milestone of 250,000 collected whole genome sequences. This accomplishment could escalate research and development of new diagnostics and therapeutic biomarkers for clinical laboratory tests and prescription drugs.
The NIH’s All of Us program “has significantly expanded its data to now include nearly a quarter million whole genome sequences for broad research use. About 45% of the data was donated by people who self-identify with a racial or ethnic group that has been historically underrepresented in medical research,” the news release noted.
Detailed information on this and future data releases is available at the NIH’s All of us Data Roadmap.
“For years, the lack of diversity in genomic datasets has limited our understanding of human health,” said Andrea Ramirez, MD, Chief Data Officer, All of Us Research Program, in the news release. Clinical laboratories performing genetic testing may look forward to new biomarkers and diagnostics due to the NIH’s newly expanded gene sequencing data set. (Photo copyright: Vanderbilt University.)
Diverse Genomic Data is NIH’s Goal
NIH launched the All of Us genomic sequencing program in 2018. Its aim is to involve more than one million people from across the country and reflect national diversity in its database.
So far, the program has grown to include 413,450 individuals, with 45% of participants self-identifying “with a racial or ethnic group that has been historically under-represented in medical research,” NIH said.
“By engaging participants from diverse backgrounds and sharing a more complete picture of their lives—through genomic, lifestyle, clinical, and social environmental data—All of Us enables researchers to begin to better pinpoint the drivers of disease,” said Andrea Ramirez, MD, Chief Data Officer of the All of Us research program, in the news release.
More than 5,000 researchers are currently registered to use NIH’s All of Us genomic database. The vast resource contains the following data:
245,350 whole genome sequences, which includes “variation at more than one billion locations, about one-third of the entire human genome.”
1,000 long-read genome sequences to enable “a more complete understanding of the human genome.”
Analysis of drugs effectiveness in different patients.
Data Shared with Participants
Participants in the All of Us program, are also receiving personalized health data based on their genetic sequences, which Dark Daily previously covered.
“Through a partnership with participants, researchers, and diverse communities across the country, we are seeing incredible progress towards powering scientific discoveries that can lead to a healthier future for all of us,” said Josh Denny, MD, Chief Executive Officer, All of Us Research Program, in the news release.
“[Researchers] can get access to the tools and the data they need to conduct a project with our resources in as little as two hours once their institutional data use agreement is signed,” said Fornessa Randal, Executive Director, Center for Asian Health Equity, University of Chicago, in a YouTube video about Researcher Workbench.
For diagnostics professionals, the growth of available whole human genome sequences as well as access to participants in the All of Us program is noteworthy.
Also impressive is the better representation of diversity. Such information could result in medical laboratories having an expanded role in precision medicine.
Executives and pathologists from many of the nation’s most prominent clinical laboratories are on their way to the Crescent City today to share best practices, hear case studies from innovative labs, and network
NEW ORLEANS—This afternoon, more than 900 lab CEOs, administrators, and pathologists will convene for the 28th Annual Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management conference. Three topics of great interest will center around adequate lab staffing, effective cost management, and developing new sources of lab testing revenue.
Important sessions will also address the explosion in next-generation sequencing and genetic testing, proposed FDA regulation of laboratory-developed tests (LDTs), and innovative ways that clinical laboratories and pathology groups can add value and be paid for that additional value.
All this is happening amidst important changes to healthcare and medicine in the United States. “Today, the US healthcare system is transforming itself at a steady pace,” explained Robert L. Michel, Editor-in-Chief of The Dark Report and Founder of the Executive War College. “Big multi-hospital health systems are merging with each other, and payers are slashing reimbursement for many medical lab tests, even as healthcare consumers want direct access to clinical laboratory tests and the full record of their lab test history.
“Each of these developments has major implications in how clinical laboratories serve their parent organizations, offer services directly to consumers, and negotiate with payers for fair reimbursement as in-network providers,” Michel added. “Attending the Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management equips lab leaders with the tools they’ll need to make smart decisions during these challenging times.”
Now in its 28th year, the Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management convenes April 25-26 in New Orleans. Executive War College extends to a third day with three full-day workshops: LEAN fundamentals for lab leaders, a genetic testing program track, and a digital pathology track. Learn more at www.ExecutiveWarCollege.com. (Photo copyright: The Dark Intelligence Group.)
Challenges and Opportunities for Clinical Laboratories
With major changes unfolding in the delivery and reimbursement of clinical services, clinical laboratory and pathology practice leaders need effective ways to respond to the evolving needs of physicians, patients, and payers. As The Dark Report has often covered, three overlapping areas are a source of tension and financial pressure for labs:
Day-to-day pressures to manage costs in the clinical laboratory or pathology practice.
The growing demand for genetic testing, accompanied by reimbursement challenges.
Evolving consumer expectations in how they receive medical care and interact with providers.
Addressing all three issues and much more, the 2023 Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management features more than 80 sessions with up to 125 lab managers, consultants, vendors, and in vitro diagnostic (IVD) experts as speakers and panelists.
Old-School Lab Rules Have Evolved into New-School Lab Rules
Tuesday’s keynote general sessions (to be reported exclusively in Wednesday’s Dark Daily ebriefing) will include four points of interest for clinical laboratory and pathology leaders who are managing change and pursuing new opportunities:
Positioning the lab to prosper by serving healthcare’s new consumers, new care models, new payment models, and more, with Michel at the podium.
How old-school lab rules have evolved into new-school lab rules and ways to transition the lab through today’s disrupters in healthcare and the clinical laboratory marketplace, with Stan Schofield, Managing Principal of the Compass Group.
Generating value by identifying risk signals in longitudinal lab data and opportunities in big data from payers, physicians, pharma, and bioresearch, with Brad Bostic, Chairman and CEO of hc1.
Wednesday’s keynote sessions (see exclusive insights in Friday’s Dark Daily ebriefing) explore:
Wednesday’s keynotes conclude with a panel discussion on delivering value to physicians, patients, and payers with lab testing services.
Clinical Labs, Payers, and Health Plans Swamped by Genetic Test Claims
Attendees of the 2023 Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management may notice a greater emphasis on whole genome sequencing and genetic testing this year.
As regular coverage and analysis in The Dark Report has pointed out, clinical laboratories, payers, and health plans face challenges with the explosion of genetic testing. Several Executive War College Master Classes will explore critical management issues of genetic and genomic testing, including laboratory benefit management programs, coverage decisions, payer relations, and best coding practices, as well as genetic test stewardship.
This year’s Executive War College also devotes a one-day intensive session on how community hospitals and local labs can set up and offer genetic tests and next-generation sequencing services. This third-day track features more than a dozen experts including:
During these sessions, attendees will be introduced to “dry labs” and “virtual CLIA labs.” These new terms differentiate the two organizations that process genetic data generated by “wet labs,” annotate it, and provide analysis and interpretation for referring physicians.
State of the Industry: Clinical Lab, Private Practice Pathology, Genetic Testing, IVD, and More
For lab consultants, executives, and directors interested in state-of-the-industry Q/A and discussions concerning commercial laboratories, private-practice pathology, and in vitro diagnostics companies, a range of breakout sessions, panels, and roundtables will cover:
Action steps to protect pathologists’ income and boost practice revenue.
Important developments in laboratory legal, regulatory, and compliance requirements.
New developments in clinical laboratory certification and accreditation, including the most common deficiencies and how to reach “assessment ready” status.
An update on the IVD industry and what’s working in today’s post-pandemic market for lab vendors and their customers.
Federal government updates on issues of concern to clinical laboratories, including PAMA, the VALID Act, and more.
Long-time attendees will notice the inclusion of “Diagnostics” into the Executive War College moniker. It’s an important addition, Michel explained for Dark Daily.
“In the recent past, ‘clinical laboratory’ and ‘anatomic pathology’ were terms that sufficiently described the profession of laboratory medicine,” he noted. “However, a subtle but significant change has occurred in recent years. The term ‘diagnostics’ has become a common description for medical testing, along with other diagnostic areas such as radiology and imaging.”
Key managers of medical laboratories, pathology groups, and in vitro diagnostics have much to gain from attending the Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management, now in its 28th year. Look for continued coverage through social media channels, at Dark Daily, and in The Dark Report.
Should their research result in new ways to identify and diagnose disease, doctors and clinical laboratories would do confirmatory testing and then initiate a precision medicine plan.
Dan Roden, MD, Senior Vice President for Personalized Medicine at VUMC and Senior Author of the Circulation study, said in a VUMC news release that the findings support the growing use of genetic information in clinical care.
“The questions we asked were: How many people who had no previous indication for cardiac genetic testing had pathogenic or likely pathogenic variants, and how many of those people actually had a phenotype in the electronic health records?” he explained.
Arrhythmia More Common than Previously Thought
The VUMC researchers drew data for their reports from the eMERGE Phase III study, which investigated the feasibility of population genomic screening by sequencing 109 genes across the spectrum of Mendelian diseases—genetic diseases that are caused by a mutation in a single gene—in more than 20,000 individuals. The scientists returned variant results to the participants and used EHR and follow-up clinical data to ascertain patient phenotypes, according to a Northwestern University Feinberg School of Medicine news release.
The research team looked specifically at the 120 consortium participants that had disease-associated pathogenic or likely pathogenic (P/LP) variants in the arrhythmia-associated genes. An analysis of the EHR data showed that 0.6% of the studied population had a variant that increases risk for potentially life-threatening arrhythmia, and that there was overrepresentation of arrhythmia phenotypes among patients, the VUMC news release noted.
The research team returned results to 54 participants and, with clinical follow-up, made 19 diagnoses (primarily long-QT syndrome) of inherited arrhythmia syndromes. Twelve of those 19 diagnoses were made only after variant results were returned, the study’s authors wrote.
Carlos G. Vanoye, PhD, Research Associate Professor of Pharmacology at Northwestern University (NU), said the study suggests arrhythmia genes may be more common than previously thought.
“A person can carry a disease-causing gene variant but exhibit no obvious signs or symptoms of the disease,” he said in the NU news release. “Because the genes we studied are associated with sudden death, which may have no warning signs, discovery of a potentially life-threatening arrhythmia gene variant can prompt additional clinical work-up to determine risks and guide preventive therapies.”
“The take-home message is that 3% of people will carry a pathogenic or likely pathogenic variant in a disease-causing gene and many others will carry variants of uncertain significance,” said Dan Roden, MD (above), Senior Vice President for Personalized Medicine at VUMC and Senior Author of the Circulation study in the VUMC news release. “We can use genetic testing, electronic health record phenotypes, and in vitro technologies to evaluate and find people who have unrecognized genetic disease and save lives by making earlier diagnoses.” Clinical laboratories will play a key role in making those early diagnoses and in managing personalized medical treatment plans. (Photo copyright: Vanderbilt University.)
Variants of Uncertain Significance
According to the NU news release, the scientists determined the functional consequences of the variants of uncertain significance they found and used that data to refine the assessment of pathogenicity. In the end, they reclassified 11 of the variants: three that were likely benign and eight that were likely pathogenic.
In the JAMA Oncology study, the VUMC scientists and other researchers conducted a phenome-wide association study to find EHR phenotypes associated with variants in 23 hereditary cancer genes. According to the VUMC news release, they identified 19 new associations:
The VUMC study findings could improve disease diagnosis and management for cancer patients and help identify high-risk individuals, the researchers noted in their published report.
In an editorial published in Circulation, titled, “First Steps of Population Genomic Medicine in the Arrhythmia World: Pros and Cons,” the professors noted that using genomic information in the case of potentially lethal inherited arrhythmia syndromes could be “lifesaving,” but questioned the benefits of reporting such secondary findings when patients are undergoing genome sequencing for other indications such as cancer.
“The likelihood that these ‘genetic diagnoses’ are translated into clinical diagnoses have not been completely evaluated,” they wrote. “In addition to the challenge of accurately identifying disease-causing genetic variants, defining the penetrance of such variants is critical to this process, i.e., what proportion of individuals in the general population with apparently pathogenic variants will develop the associated phenotype? If penetrance is low for particular gene/phenotype combinations, the costs associated with clinical screening and the psychological effects on individuals informed that they have potentially life-threatening variants may outweigh the benefits of the few new clinical diagnoses.”
These latest studies provide further evidence of the value of big data in healthcare and offer another lesson to clinical laboratories and pathologist about the future role data streaming from clinical laboratories and pathology assays may have in the growth of personalized medicine.
Study shows that access to early childhood treatment could have lasting effects and prevent premature adult aging
Researchers in New Zealand have found that people who experienced “daily smoking status, obesity, or a psychological disorder diagnosis” beginning early in life were “biologically older” at midlife than those who did not. The findings suggest that early access to treatments for these health concerns could decrease risk for “accelerated biological aging,” according to the study published in JAMA Pediatrics.
Although these findings do not currently provide a path to a diagnostic test for clinical laboratories, this study is yet another example of how researchers are increasingly using broad swaths of healthcare data to help identify people at risk for certain healthcare conditions.
Such research often presents opportunities for medical laboratories to participate in healthcare Big Data analysis, which in turn helps healthcare providers make precision medicine diagnoses for individual patients.
Study Assessments and Clinical Laboratory Biomarkers
The scientists found that participants who had one of three health conditions as an adolescent—obesity, smoking daily, or psychological disorder (anxiety, attention deficit/hyperactivity disorder, depression)—showed advanced signs of aging at age 45 when compared to others without those conditions, CNN reported.
The signs included:
Walking 11.2 centimeters per second slower.
Brain appears 2.5 years older.
Face appears four years older.
At age 11, 13, and 15, the Dunedin Study participants were assessed by pulmonary specialists and others for asthma, cigarette smoking, and obesity, Fox News reported.
“There’s a long history of that kind of research in terms of how smoking is damaging at the cellular level but also can result in the kinds of health conditions that we associate with biological aging, like (chronic obstructive pulmonary disease), lung cancer, things like that,” the study’s first author Kyle Bourassa, PhD (above), told CNN. “The hope is if we were to study a cohort now, a much higher proportion of those children and adolescents are actually going to be treated for these things, which will reduce the risk of accelerated aging later in life,” he added. Results of the study may also lead to new clinical laboratory diagnostics. (Photo copyright: Duke University.)
According to an earlier DMHDRU statement, the biomarkers used at this point in the study included:
“Participants who had smoked daily, had obesity, or had a psychological disorder diagnosis during adolescence were biologically older at midlife compared with participants without these conditions. Participants with asthma were not biologically older at midlife compared with those without asthma,” the researchers wrote. These findings led the researchers to certain conclusions about receiving early treatments, CNN reported.
“No participants in this cohort were prescribed stimulants for attention-deficit/hyperactivity disorder, and selective serotonin reuptake inhibitors were not yet in use for adolescent depression and anxiety during the study period. Whereas 81.1% of the adolescents with asthma received some type of treatment, which could have mitigated the implications for biological aging,” the authors wrote in their study.
“Our paper reaffirms that those are important treatments and those kinds of investments younger in the lifespan could net big benefits in terms of both health and the cost of healthcare later on as well,” Kyle Bourassa, PhD, told CNN. Bourassa is the study’s First Author and a clinical psychology researcher and advanced research fellow at the Durham VA Health Care System.
Clinical Laboratories Curate Massive Amounts of Healthcare Data
For pathologists and medical laboratory scientists, the University of Otago study is a reminder that clinical laboratories provide a critical tool to diagnostics professionals: housing, sharing, and analyzing data that contribute to precision medicine diagnoses.
The DMHDRU researchers’ findings also highlight the importance of access to common treatments offered early in life for some people to reduce risk of accelerated aging and disease.
Though the variant poses low risk thanks to modern HIV treatments, the scientists stress the importance of access to early clinical laboratory testing for at-risk individuals
With the global healthcare industry hyper focused on arrival of the next SARS-CoV-2 variant, pathologists and clinical laboratories may be relieved to learn that—though researchers in the Netherlands discovered a previously unknown “highly virulent” strain of HIV—the lead scientist of the study says there’s “no cause for alarm.”
In a news release, researchers at the University of Oxford Big Data Institute said the HIV variant got started in the Netherlands in the 1990s, spread quickly into the 2000s, and that prior to treatment, people with the new virulent subtype B (VB variant) had exceptionally high viral loads compared to people with other HIV variants.
Fortunately, the scientist also found that around 2010, thanks to antiretroviral drug therapy, the severe variant began to decline.
In an interview with NPR, Chris Wymant, PhD, the study’s lead author, said, “People with this variant have a viral load that is three to four times higher than usual for those with HIV. This characteristic means the virus progresses into serious illness twice as fast, and also makes it more contagious.”
Fortunately, he added, “Existing medications work very well to treat even very virulent variants like this one, cutting down on transmission and reducing the chance of developing severe illness.
“Nobody should be alarmed,” he continued. “It responds exactly as well to treatment as HIV normally does. There’s no need to develop special treatments for this variant.”
Wymant is senior researcher in statistical genetics and pathogen dynamics at the Big Data Institute (BDI).
Epidemiologist Chris Wymant, PhD (above), lead author of the Big Data Institute study at Oxford University, says today’s modern HIV antiretroviral drug therapies effectively treat for the “highly viral” HIV VB variant he and his team discovered. “Nobody should be alarmed,” he told NPR. “It responds exactly as well to treatment as HIV normally does.” Nevertheless, he stressed the importance of access to early clinical laboratory testing for at-risk individuals. (Photo copyright: Oxford Big Data Institute.)
In their published study, the BDI researchers reported that their analysis of genetic sequences of the VB variant suggested it “arose in the 1990s from de novo (of new) mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.
“By the time, they were diagnosed, these individuals were vulnerable to developing AIDS within two to three years. The virus lineage, which has apparently arisen de novo since around the millennium, shows extensive change across the genome affecting almost 300 amino acids, which makes it hard to discern the mechanism for elevated virulence,” the researchers noted.
The researchers analyzed a data set from the project BEEHIVE (Bridging the Epidemiology and Evolution of HIV in Europe and Uganda). They found 15 of 17 people positive for the VB variant residing in the Netherlands. That prompted them to focus on a cohort of more than 6,700 Dutch HIV positive people in the ATHENA (AIDS Therapy Evaluation in the Netherlands) cohort database, where they found 92 more individuals with the VB variant, bringing the total to 109.
According to a Medscape report on the study’s findings, people with the VB variant showed the following characteristics:
Double the rate of CD4-positive T-cell declines (indicator of immune system damage by HIV), compared to others with subtype-B strains.
Increased risk of infecting others with the virus based on transmissibility associated with variant branching.
Wymant says access to clinical laboratory testing is key to curtailing the number of people who contract the VB variant. “Getting people tested as soon as possible, getting them onto treatment as soon as possible, has helped reduce the numbers of this variant even though we didn’t know that it existed,” he told NPR.
The University of Oxford Big Data Institute study is another example of how constantly improving genome sequencing technology allows scientists to dig deeper into genetic material for insights that can advance the understanding of many diseases and health conditions.
