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.
Findings could lead to deeper understanding of why we age, and to medical laboratory tests and treatments to slow or even reverse aging
Can humans control aging by keeping their genes long and balanced? Researchers at Northwestern University in Evanston, Illinois, believe it may be possible. They have unveiled a “previously unknown mechanism” behind aging that could lead to medical interventions to slow or even reverse aging, according to a Northwestern news release.
Should additional studies validate these early findings, this line of testing may become a new service clinical laboratories could offer to referring physicians and patients. It would expand the test menu with assays that deliver value in diagnosing the aging state of a patient, and which identify the parts of the transcriptome that are undergoing the most alterations that reduce lifespan.
It may also provide insights into how treatments and therapies could be implemented by physicians to address aging.
“I find it very elegant that a single, relatively concise principle seems to account for nearly all of the changes in activity of genes that happen in animals as they change,” Thomas Stoeger, PhD, postdoctoral scholar in the Amaral Lab who led the study, told GEN. Clinical laboratories involved in omics research may soon have new anti-aging diagnostic tests to perform. (Photo copyright: Amaral Lab.)
Possible ‘New Instrument’ for Biological Testing
Researchers found clues to aging in the length of genes. A gene transcript length reveals “molecular-level changes” during aging: longer genes relate to longer lifespans and shorter genes suggest shorter lives, GEN summarized.
The phenomenon the researchers uncovered—which they dubbed transcriptome imbalance—was “near universal” in the tissues they analyzed (blood, muscle, bone, and organs) from both humans and animals, Northwestern said.
According to the National Human Genome Research Institute fact sheet, a transcriptome is “a collection of all the gene readouts (aka, transcript) present in a cell” shedding light on gene activity or expression.
The Northwestern study suggests “systems-level” changes are responsible for aging—a different view than traditional biology’s approach to analyzing the effects of single genes.
“We have been primarily focusing on a small number of genes, thinking that a few genes would explain disease,” said Luis Amaral, PhD, Senior Author of the Study and Professor of Chemical and Biological Engineering at Northwestern, in the news release.
“So, maybe we were not focused on the right thing before. Now that we have this new understanding, it’s like having a new instrument. It’s like Galileo with a telescope, looking at space. Looking at gene activity through this new lens will enable us to see biological phenomena differently,” Amaral added.
In their Nature Aging paper, Amaral and his colleagues wrote, “We hypothesize that aging is associated with a phenomenon that affects the transcriptome in a subtle but global manner that goes unnoticed when focusing on the changes in expression of individual genes.
“We show that transcript length alone explains most transcriptional changes observed with aging in mice and humans,” they continued.
In tissues studied, older animals’ long transcripts were not as “abundant” as short transcripts, creating “imbalance.”
“Imbalance” likely prohibited the researchers’ discovery of a “specific set of genes” changing.
As animals aged, shorter genes “appeared to become more active” than longer genes.
In humans, the top 5% of genes with the shortest transcripts “included many linked to shorter life spans such as those involved in maintaining the length of telomeres.”
Conversely, the researchers’ review of the leading 5% of genes in humans with the longest transcripts found an association with long lives.
Antiaging drugs—rapamycin (aka, sirolimus) and resveratrol—were linked to an increase in long-gene transcripts.
“The changes in the activity of genes are very, very small, and these small changes involve thousands of genes. We found this change was consistent across different tissues and in different animals. We found it almost everywhere,” Thomas Stoeger, PhD, postdoctoral scholar in the Amaral Lab who led the study, told GEN.
In their paper, the Northwestern scientists noted implications for creation of healthcare interventions.
“We believe that understanding the direction of causality between other age-dependent cellular and transcriptomic changes and length-associated transcriptome imbalance could open novel research directions for antiaging interventions,” they wrote.
While more research is needed to validate its findings, the Northwestern study is compelling as it addresses a new area of transcriptome knowledge. This is another example of researchers cracking open human and animal genomes and gaining new insights into the processes supporting life.
For clinical laboratories and pathologists, diagnostic testing to reverse aging and guide the effectiveness of therapies may one day be possible—kind of like science’s take on the mythical Fountain of Youth.
Research could lead to new microbiome assays that clinical laboratories could use to identify genetic and other health conditions in developing baby
It would seem to be common sense, but now a study conducted by the Broad Institute of MIT and Harvard confirms that a pregnant mother’s microbiome has an effect on the development of her baby’s own gut microbiota. These findings could create opportunities for clinical laboratories to help in diagnosing a broader range of health conditions by testing the gut bacteria of pregnant mothers.
The Broad Institute’s study suggests the mother’s gut microbiome helps form the baby’s gut bacteria not only during pregnancy and birth, but into the baby’s first year of life as well.
“This study helps us better understand how the rich community of microbes in the gut initially forms and how it develops during infancy,” said Tommi Vatanen, PhD, a co-first author on the study who is now a researcher and associate professor at the University of Helsinki, in a Broad Institute news release. “The microbiome is very dynamic and develops along with other systems, so there’s a lot going on in the first years of life.”
“We’ve shown that the maternal microbiome plays an important role in seeding the infant microbiome, and that it’s not a one-time event, but a continuous process,” said gastroenterologist and senior study author Ramnik Xavier, MD, of the Broad Institute. Clinical laboratories and microbiologists may soon have new tools for testing a mother’s microbiome during pregnancy. (Photo copyright: Maria Nemchuk, Broad Institute.)
Study Highlights Physiological Connection Between Mother and Child
This study, according to the Broad Institute news release, is the “first to uncover large-scale horizontal gene transfer events between different species of maternal and infant gut bacteria.” The researchers also found that the bacteria in the mother’s microbiome “donate” genes that go into the bacteria of her unborn child. The mother’s genes help the baby in other ways as well during pregnancy and after birth.
“Benign bacteria in the maternal gut share genes with the child’s intestinal microbes during early life, potentially contributing to immune and cognitive development,” states the news release, adding, “The microbiomes of the mother and baby change during pregnancy and the first year of life … some bacteria in the mother’s gut donate hundreds of genes to bacteria in the baby’s gut. These genes are involved in the development of the immune and cognitive systems and help the baby to digest a changing diet as it grows.”
The study also sheds light on a baby’s unique metabolites (chemicals produced by bacteria) and how they connect with the mother’s microbiome.
“This is the first study to describe the transfer of mobile genetic elements between maternal and infant microbiomes,” gastroenterologist Ramnik Xavier, MD, Core Institute Member, Director of the Immunology Program, and Co-Director of the Infectious Disease and Microbiome Program at the Broad Institute, told Neuroscience News.
“Our study also, for the first time, integrated gut microbiome and metabolomics profiles from both mothers and infants and discovered links between gut metabolites, bacteria, and breastmilk substrates,” he added.
Researchers Use Multiomics
The human microbiome influences health in many ways. For several years, Broad Institute scientists have been trying to better understand the human microbiome and the role it plays in diseases like type 1 diabetes, cancer, and inflammatory bowel disease.
According to the organization’s website, the scientists recently began using multiomics techniques in their research that include:
Xavier and his colleagues were particularly interested in the development of the microbiome during the first year of the baby’s life.
“The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites,” the researchers wrote in Cell. “Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to one year of age using longitudinal multiomics data.”
The researchers deployed bacterial DNA sequencing from stool samples of 70 mother and child pairs.
They found “hundreds of genes” in the infant gut bacterial genome that originated in the mother. According to the scientists, this suggests a mother does not transfer her genes all at once during childbirth. Instead, it likely occurs in an “ongoing” gene transfer from mother to baby through the baby’s first year of life, the news release explains.
Here are details on the study findings, according to Neuroscience News:
Genes associated with diet were involved in the “mother-to-infant interspecies transfer of mobile genetic elements.”
Infant gut metabolomes were less diverse than maternal metabolomes.
Infants had 2,500 unique metabolites not detected in the mothers.
Infants that received baby formula had distinct metabolites and cytokine signatures as compared to those receiving breast milk.
A link between pregnancy and an increase in steroid compounds could be due to impaired glucose tolerance in mothers.
“We also found evidence that prophages—dormant bacteriophages (viruses that reside on bacterial genomes)—contribute to the exchange of mobile genetic elements between maternal and infant microbiomes,” Xavier told Neuroscience News.
Research Could Lead to New Clinical Laboratory Assays
Microbiologists and clinical laboratory scientists are gaining a deeper understanding of the role gut bacteria play in many aspects of human life. But how a mother’s microbiome influences a baby’s development during and after birth is particularly intriguing.
“We’ve shown that the maternal microbiome plays an important role in seeding the infant microbiome, and that it’s not a one-time event, but a continuous process,” said Xavier in the Broad Institute news release. “This may be yet another benefit of prolonged bonding between mother and child, providing more chances for these beneficial gene transfer events to occur.”
Pediatricians, microbiologists, and clinical laboratories may one day have new microbiome assays to help identify a broad range of health conditions in mothers and infants and explore gut bacteria’s effects on a baby’s developing health.
The speakers also noted that labs must learn to work collaboratively with payers—perhaps through health information technology (HIT)—to establish best practices that improve reimbursements on claims for novel genetic tests.
Harnessing the ever-increasing volume of diagnostic data that genetic testing produces should be a high priority for labs, said William Morice II, MD, PhD, CEO and President of Mayo Clinic Laboratories.
“There will be an increased focus on getting information within the laboratory … for areas such as genomics and proteomics,” Morice told the keynote audience at the Executive War College on Wednesday.
“Wearable technology data is analyzed using machine learning. Clinical laboratories must participate in analyzing that spectrum of diagnostics,” said William Morice II, MD, PhD (above), CEO and President of Mayo Clinic Laboratories. Morice spoke during this week’s Executive War College.
Precision Medicine Efforts Include Genetic Testing and Wearable Devices
For laboratories new to genetic testing that want to move it in-house, Morice outlined effective first steps to take, including the following:
Determine and then analyze the volume of genetic testing that a lab is sending out.
Research and evaluate genetic sequencing platforms that are on the market, with an eye towards affordable cloud-based options.
Build a business case to conduct genetic tests in-house that focuses on the long-term value to patients and how that could also improve revenue.
A related area for clinical laboratories and pathology practices to explore is their role in how clinicians treat patients using wearable technology.
For example, according to Morice, Mayo Clinic has monitored 20,000 cardiac patients with wearable devices. The data from the wearable devices—which includes diagnostic information—is analyzed using machine learning, a subset of artificial intelligence.
In one study published in Scientific Reports, scientists from Mayo’s Departments of Neurology and Biomedical Engineering found “clear evidence that direct seizure forecasts are possible using wearable devices in the ambulatory setting for many patients with epilepsy.”
Clinical laboratories fit into this picture, Morice explained. For example, depending on what data it provides, a wearable device on a patient with worsening neurological symptoms could trigger a lab test for Alzheimer’s disease or other neurological disorders.
“This will change how labs think about access to care,” he noted.
For Payers, Navigating Genetic Testing Claims is Difficult
While there is promise in genetic testing and precision medicine, from an administrative viewpoint, these activities can be challenging for payers when it comes to verifying reimbursement claims.
“One of the biggest challenges we face is determining what test is being ordered. From the perspective of the reimbursement process, it’s not always clear,” said Cristi Radford, MS, CGC, Product Director at healthcare services provider Optum, a subsidiary of UnitedHealth Group, located in Eden Prairie, Minnesota. Radford also presented a keynote at this year’s Executive War College.
Approximately 400 Current Procedural Terminology (CPT) codes are in place to represent the estimated 175,000 genetic tests on the market, Radford noted. That creates a dilemma for labs and payers in assigning codes to novel genetic tests.
During her keynote address, Radford showed the audience of laboratory executives a slide that charted how four labs submitted claims for the same high-risk breast cancer panel. CPT code choices varied greatly.
“Does the payer have any idea which test was ordered? No,” she said. “It was a genetic panel, but the information doesn’t give us the specificity payers need.”
In such situations, payers resort to prior authorization to halt these types of claims on the front end so that more diagnostic information can be provided.
“Plans don’t like prior authorization, but it’s a necessary evil,” said Jason Bush, PhD, Executive Vice President of Product at Avalon Healthcare Solutions in Tampa, Florida. Bush co-presented with Radford.
[Editor’s note: Dark Daily offers a free webinar, “Learning from Payer Behavior to Increase Appeal Success,” that teaches labs how to better understand payer behavior. The webinar features recent trends in denials and appeals by payers that will help diagnostic organizations maximize their appeal success. Click here to stream this important webinar.]
Payers Struggle with ‘Explosion’ of Genetic Tests
In “UnitedHealth’s Optum to Offer Lab Test Management,” Dark Daily’s sister publication The Dark Report, covered Optum’s announcement that it had launched “a comprehensive laboratory benefit management solution designed to help health plans reduce unnecessary lab testing and ensure their members receive appropriate, high-quality tests.”
Optum sells this laboratory benefit management program to other health plans and self-insured employers. Genetic test management capabilities are part of that offering.
As part of its lab management benefit program, Optum is collaborating with Avalon on a new platform for genetic testing that will launch soon and focus on identifying test quality, streamlining prior authorization, and providing test payment accuracy in advance.
“Payers are struggling with the explosion in genetic testing,” Bush told Executive War College attendees. “They are truly not trying to hinder innovation.”
For clinical laboratory leaders reading this ebriefing, the takeaway is twofold: Genetic testing and resulting precision medicine efforts provide hope in more effectively treating patients. At the same time, the genetic test juggernaut has grown so large so quickly payers are finding it difficult to manage. Thus, it has become a source of continuous challenge for labs seeking reimbursements.
Heath information technology may help ease the situation. But, ultimately, stronger communication between labs and payers—including acknowledgement of what each side needs from a business perspective—is paramount.
From ‘new-school’ rules of running a clinical laboratory to pharmacy partnerships to leveraging lab data for diagnostics, key industry executives discussed the new era of clinical laboratory and pathology operations
Opening keynotes at the 28th Annual Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management taking place in New Orleans this week covered three main forces that healthcare and medical laboratory administrators should be preparing to address: new consumer preferences, new care models, and new payment models.
“COVID-19 didn’t change a whole lot of things in one sense, but it accelerated a lot of trends that were already happening in healthcare,” said Robert L. Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report, and Founder of the Executive War College, during his opening keynote address to a packed ballroom of conference attendees. “Healthcare is transforming, and the transformation is far more pervasive than most consumers appreciate.
“Disintermediation, for example, is taking traditional service providers and disrupting them in substantial ways, and if you think about the end of fee-for-service, be looking forward because your labs can be paid for the value you originate that makes a difference in patient care,” Michel added.
Another opportunity for clinical laboratories, according to Michel, is serving Medicare Advantage plans which have soared in enrollment. “Lab leaders should be studying Medicare Advantage for how to integrate Medicare Advantage incentives into their lab strategies,” he said, highlighting the new influence of risk adjustment models which use diagnostic data to predict health condition expenditures.
Opening sessions at this week’s annual Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management, presented by Robert L. Michel (above), Editor-in-Chief of Dark Daily and its sister publication The Dark Report, discussed demand for delivering healthcare services—including medical laboratory testing—as consumer preferences evolve, new care models are designed, and as payers seek value over volume. While these three forces may be challenging at the outset, they also create opportunities for clinical laboratories and pathology groups—a focal point of the Executive War College each year. (Photo copyright: The Dark Intelligence Group.)
Medical Laboratories Must Adapt to ‘New-School’ Rules
During his keynote address, Stan Schofield, Vice President and Managing Principal at The Compass Group, noted that while the basic “old-school” rules of successfully running a clinical laboratory have not changed—e.g., adding clients, keeping clients, creating revenue opportunities, getting paid, and reducing expenses—the interpretation of each rule has changed. The Compass Group is a trade federation based in South Carolina that serves not-for-profit healthcare integrated delivery networks (IDNs), including 32 health systems and 600 hospitals.
Schofield advised that when it comes to adding new clients under the “new-school” rules of lab management, clinical laboratory directors must be aware of and adapt to hospital integrations of core labs, clinical integrations across health systems, seamless services, direct contracting with employers in insurance relationships, and direct-to-consumer testing. Keeping clients, Schofield said, involves five elements:
Strong customer service.
A tailored metrics program for quality services based on what is important to a lab’s clients.
Balanced scorecards that look at the business opportunity and value proposition with each client.
Monitoring patients’ experiences and continuous improvement.
Participation in all payer agreements.
As to the problem of commoditization of laboratory goods and services, Schofield said, “Right now, we’re facing the monetization of the laboratory. We’re going to swiftly move from commoditization to monetization to commercialization.”
Pharmacies Enter the Clinical Laboratory Market
In another forward looking keynote address, David Pope, PharmD, CDE, Chief Pharmacy Officer at OmniSYS, XiFin Pharmacy Solutions, discussed the “test to treat” trend which could bring clinical laboratories and pharmacies together in new partnerships.
Diagnostics and pharmacy now intersect, according to Pope. “Pharmacists are on the move, and they are true contender as a new provider for you,” he said. “An area of pharmacy that is dependent upon labs is specialty medications.”
Specialty medicines now account for 55% of prescription spending, up from 28% in 2011, driven by growth in auto-immune and oncology, Pope noted. Other examples include companion diagnostics required for targeted treatments pertaining to all major cancers, and new areas like thalassemia (inherited blood disorders), obesity, next-generation sequencing, and pharmacogenomics, in addition to routine testing such as liver function and complete blood count (CBC).
Federal legislation may soon recognize pharmacists as healthcare providers who will be trained to perform specific clinical services, Pope said. Some states already recognize pharmacists as providers, he noted, explaining that pharmacies need lab data for three primary reasons:
Service—Pharmacies can act as a referral source to clinical laboratories. When referring, pharmacies may need to communicate lab test results to patients or providers to coordinate care.
Value-based care—Pharmacies would draw on data to counsel, prescribe, and coordinate care for chronic disease management, among other services.
Diagnostics and pharmacogenetics—Specialty medication workflows require documented test results within a specific timeframe prior to dispensing.
Another point Pope made: Large pharmacies are seeking lab partners. Labs that can provide rapid turnaround time and good pricing on complex tests provide pharmacies with partnership opportunities.
Using AI to Create Patients’ ‘Digital Twins’ That Help Identify Disease and Improve Care
High-tech healthcare technology underlies many opportunities in the clinical laboratory and pathology market, as evidenced throughout the Executive War College’s 2023 curriculum. An ongoing challenge for labs, however, is how to produce the valuable datasets that all labs have the potential to generate.
“It feels like we’ve come so far,” explained Brad Bostic, CEO of hc1 during his keynote address. “We’ve got the internet. We’ve got the cloud. All of this is amazing, but in reality, we have this massive proliferation of data everywhere and it’s very difficult to know how to actually put that into use. And nobody’s generating more data than clinical laboratories.
“Every single interaction with a patient that generates data gives you this opportunity to create the idea of a ‘digital twin.’ That means that labs are creating a mathematical description of what a person’s state is and using that information to look at how providers can optimally diagnose and treat that person. Ultimately, it is bigger than just one person. It’s hundreds of millions of people that are generating all this data, and many of these people fall into similar cohorts.”
This digital twin opportunity is heavily fueled by medical laboratory testing, Bostic said, adding that labs need to be able to leverage artificial intelligence (AI) to:
“I recommend lab leaders sit down with their teams and any outside partners they trust and identify what are their lab’s goals,” Bostic stated. “Think about how this technology can advance a lab’s mission. Look at strategy holistically—everything from internal operations to how patient care is affected.”
