The research also could lead to a better understanding of how short tandem repeats (STRs)—the number of times a gene is copied into RNA for protein use—affect gene expression as well, according to Stanford.
“We’ve known for a while that short tandem repeats or STRs, aren’t junk because their presence or absence correlates with changes in gene expression. But we haven’t known how they exert these effects,” said study lead Polly Fordyce, PhD (above), Associate Professor of Bioengineering and Genetics at Stanford University, in a news release. The research could lead to new clinical laboratory biomarkers for genetic testing. (Photo copyright: Stanford University.)
“Researchers have spent a lot of time characterizing these transcription factors and figuring out which sequences—called motifs—they like to bind to the most,” said the study lead Polly Fordyce, PhD, Associate Professor of Bioengineering and Genetics at Stanford University, in a Stanford Medicine news release.
“But current models don’t adequately explain where and when transcription factors bind to non-coding DNA to regulate gene expression. Sometimes, no transcription factor is attached to something that looks like a perfect motif. Other times, transcription factors bind to stretches of DNA that aren’t motifs,” the news release explains.
Transcription factors are “like light switches that can turn genes on or off depending on what cells need,” notes a King’s College LondonEDIT Labblog post.
But why do transcription factors target some places in the genome and not others?
“To solve the puzzle of why transcription factors go to some places in the genome and not to others, we needed to look beyond the highly preferred motifs,” Fordyce added. “In this study, we’re showing that the STR sequence around the motif can have a really big effect on transcription factor binding, providing clues as to what these repeated sequences might be doing.”
Such information could aid in understanding certain hereditary conditions and diseases.
“Variations in STR length have been associated with changes in gene expression and implicated in several complex phenotypes such as schizophrenia, cancer, autism, and Crohn’s disease. However, the mechanism by which STRs affect transcription remains unknown,” the researchers wrote in Science.
Special Assays Explore Binding
According to their paper, the research team turned to the Fordyce Lab’s previously developed microfluidic binding assays (MITOMI, k–MITOMI, and STAMMP) to analyze the impact of different DNA sequences on transcription factor binding.
“In the experiment we asked, ‘How do these changes impact the strength of transcription factor binding?’ We saw a surprisingly large effect. Varying the STR sequence around a motif can have a 70-fold impact on the binding,” Fordyce wrote.
“This research unveils, for the first time, the intricate connection between how variants in the non-coding genome affect genes that are associated with blood pressure and with hypertension. What we’ve created is a kind of functional map of the regulators of blood pressure genes, “said Philipp Maass, PhD, Lead Researcher and Assistant Professor Molecular Genetics, University of Toronto, in a news release.
The findings could aid precision medicine for cardiovascular health and may possibly be adopted to other conditions, according to The Hospital for Sick Children.
“The variants we have characterized in the non-coding genome could be used as genomic markers for hypertension, laying the groundwork for future genetic research and potential therapeutic targets for cardiovascular disease,” Maass noted.
Why All the ‘Junk’ DNA?
Clinical laboratory scientists may wonder why genetic research has primarily focused on 20,000 genes within the genome, leaving the “junk” DNA for later investigation. So did researchers at Harvard University.
“After the Human Genome Project, scientists found that there were around 20,000 genes within the genome, a number that some researchers had already predicted. Remarkably, these genes comprise only about 1-2% of the three billion base pairs of DNA. This means that anywhere from 98-99% of our entire genome must be doing something other than coding for proteins,” they wrote in a blog post.
“Imagine being given multiple volumes of encyclopedias that contained a coherent sentence in English every 100 pages, where the rest of the space contained a smattering of uninterpretable random letters and characters. You would probably start to wonder why all those random letters and characters were there in the first place, which is the exact problem that has plagued scientists for decades,” they added.
Not only is junk DNA an interesting study subject, but ongoing research may also produce useful new biomarkers for genetic diagnostics and other clinical laboratory testing. Thus, medical lab professionals may want to keep an eye on new developments involving non-coding DNA.
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.
“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.”
“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.
Demand for low cost, convenient access to doctors and drugs is driving transformation to decentralized medical care, and retail pharmacy chains see opportunity in offering primary care services
Retail pharmacies and pharmacists continue to play a growing role in healthcare as consumer demand for lower cost and convenience pushes the nation’s medical landscape away from centralized healthcare systems. Clinical laboratories have seen this in the increasing trend of consumers seeking vaccinations and home-health tests at their local drug stores.
Results of a pair of surveys dubbed “Pharmacy Next” conducted by Wolters Kluwer Health revealed that 58% of people are now willing to be treated for non-emergency healthcare conditions in non-traditional medical environments, such as retail pharmacies and clinics.
This is a finding that clinical laboratory managers and pathologists should incorporate into their labs’ strategic planning. It portends a shift in care away from the traditional primary care clinic—typically located in the campus around the community hospital—and toward retail pharmacies. Labs will want to capture the test referrals originating from the primary care clinics located in retail pharmacies.
This willingness to access medical care in non-traditional environments is especially true among people in Generation Y (Millennials) and Generation Z (Zoomers)—people born between 1981-1996 (Gen Y) and 1997-2012 (Gen Z), according to Journey Matters.
“As we saw in last year’s survey, primary care decentralization is continuing—the traditional one doctor-one patient, single point of coordination is vanishing, and this is especially evident in younger generations,” said Peter Bonis, MD, Wolters Kluwer’s Chief Medical Officer, in a press release.
The online surveys of more than 2,000 US adults was weighted by age, gender, household income, and education to be representative of the entire population of the United States.
“By preparing for this shift today, providers can work in concert across care sites to deliver the best care to patients,” said Peter Bonis, MD, Wolters Kluwer Health Chief Medical Officer, in a press release. “Likewise, newer care delivery models, like retail pharmacies and clinics, can ensure they’re ready to meet the expectations of healthcare consumers, who will increasingly be turning to them for a growing range of care needs.” Clinical laboratories may find new revenue opportunities working with the primary care clinics operating within local retail pharmacists and clinicians. (Photo copyright: Wolters Kluwer.)
Key Findings of the Wolters Kluwer Pharmacy Next Studies
Some key insights of the surveys include:
Care is rapidly decentralizing with 58% stating they are likely to visit a local pharmacy for non-emergency medical care.
Younger generations are signaling lasting change within the industry as they are more open to non-traditional styles of care.
61% of respondents envision most primary care services being provided at pharmacies, retail clinics, or pharmacy clinics within the next five years. Of the respondents, 70% of Millennials, 66% of Gen Z, 65% of Gen X, and 43% of Baby Boomers believe this transition will occur.
Consumers are worried about prescription costs and availability.
92% of respondents said physicians and pharmacists should inform patients of generic options.
59% of surveyed consumers have concerns about drug tampering and theft when it involves mail order or subscription prescription services.
One in three respondents believe convenience is more important than credentials in non-emergency situations.
The survey indicates that healthcare consumers across multiple generations are open to a shift in some medical services from doctors to pharmacists. However, there were some notable differences between generations.
Respondents of the Baby Boomer (55%) and Gen X (57%) generations stated they would trust a physician assistant with medication prescriptions, while only 42% of Gen Z and 47% of Millennial respondents felt the same way.
Additionally, Boomers (57%) and Gen X (67%) said they would feel comfortable with a nurse practitioner issuing their prescriptions, while only 44% of Gen Z and 53% of Millennials said they would.
Increased Comfort with Genetic Testing at Pharmacies
Overall, 68% of individuals polled believe their individual genomic data could guide prescription decisions, with Millennials (77%) and Gen Z (74%) being the primary believers. Additionally, 88% of respondents stated they see an incentive for health insurers to cover genomic testing, and 72% said they would be open to genetic testing for personalized medical care.
But pharmacists and clinicians should be aware that advancing pharmacogenomics will require addressing privacy concerns. According to the Wolters Kluwer study, 57% of Gen Z and 53% of Millennials have apprehension surrounding genetic testing due to privacy risks, with 35% of Gen X and Boomers holding that same opinion.
Healthcare Staff Shortages, Drug Cost a Concern
Survey respondents are also concerned about pharmacy staff shortages and expenditures when seeking care at a pharmacy. Half of the participants are worried they will receive the wrong medication, half worry about getting the incorrect dosage, and almost half (47%) fear receiving the wrong directions due to overburdened pharmacy employees.
More people in Gen Z (59%) and Millennials (60%) had these concerns compared to Gen X (44%) and Boomers (38%).
Sadly, a distressing 44% of those surveyed admitted to not filling a prescription due to the costs. That number jumps to a staggering 56% among individuals with no health insurance, compared to 42% for insured patients.
“From hospitals to doctors’ offices, from pharmacies to pharma and beyond, healthcare must move to more affordable and accessible primary care models, adopt innovations that help deliver more personalized care, and address persistent safety and cost concerns that consumers have about their medications,” said Bonis in the press release.
Can Pharmacies Deliver Primary Care as Well as Doctor’s Offices?
Pharmacies may be logical setting for at least some non-emergency health services. According to the Centers for Disease Control and Prevention (CDC), approximately 90% of the US population live within five miles of a pharmacy and about 72% of visits to physician’s offices involve the prescribing and monitoring of medication therapies.
“We’re not talking about complicated services. We’re talking low-acuity, very basic care,” said Anita Patel, PharmD, Vice President of Pharmacy Services Development for Walgreens, at the HIMSS conference.
Pharmacies across the country continue to add more healthcare services to their available public offerings. This trend will likely persist into the future as healthcare becomes more expensive, wait times for physician appointments increases, and medical staff shortages rise. Thus, there may be opportunities for clinical laboratories to support pharmacists and doctors working in retail settings.
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.
“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.
[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.
There was cautious optimism about the ability of Canada’s medical laboratories to innovate in ways that advance patient care, while recognizing the ongoing challenge of adequate lab staffing and budget constraints
TORONTO, ONTARIO, CANADA—This week, more than 150 leaders representing clinical laboratories, anatomic pathology labs, in vitro diagnostics (IVD) companies, and provincial health officials gathered for the first “Canadian Diagnostic Executive Forum” (CDEF) since 2019. It would be apt to say that the speakers objectively addressed all the good, the bad, and the ugly of Canada’s healthcare system and its utilization of medical laboratory testing services.
Over the two days of the conference, speakers and attendees alike concurred that the two biggest issues confronting clinical laboratories in Canada were inadequate staffing and an unpredictable supply chain. There also was agreement that the steady increase in prices, fueled by inflation, is exacerbating continuing cost increases in both lab salaries and lab supplies.
Canada’s Health System Has Several Unique Attributes
Canada’s healthcare system has two unique attributes that differentiate it from those of other nations. First, healthcare is mandated by a federal law, but generally each of Canada’s 13 provinces and territories operates its own health plan. Thus, the health system in each province and territory may cover a different mix of clinical services, therapeutic drugs, and medical procedures. The federal government typically pays 40% of a province’s health costs and the province funds the balance.
Second, it is a fact that 90% of the Canadian population lives within 150 miles of the United States border. Yet there are provinces with large populations that have geography that ranges from the US border to north of the Arctic Circle. These provinces have a major challenge to ensure equal access to healthcare regardless of where their citizens live.
During day one of the conference, several presentations addressed innovations that supported those labs’ efforts to deliver value and timely insights during the COVID-19 pandemic. For example, a lab team in Alberta launched a research study involving SARS-CoV-2 virus surveillance from the earliest days of the outbreak. This study was presented by Mathew Diggle, PhD, FRCPath, Associate Professor and Program Lead for the Public Health Laboratory (ProvLab) Medical-Scientific Staff at Alberta Precision Laboratories in Edmonton, Alberta.
Study Designed to Identify Coinfections with COVID-19
While performing tens of thousands of COVID-19 tests from the onset of the pandemic, and identifying the emergence of variants, the ProvLab team also tracked co-infection involving other respiratory viruses.
“This is one of the largest eCoV [endemic coronavirus] studies performed during the COVID-19 pandemic,” Diggle said. “This broad testing approach helped to address a pivotal diagnostic gap amidst the emergence of a novel pathogen: cross-reactivity with other human coronaviruses that can cause similar clinical presentations. This broad surveillance enabled an investigation of cross-reactivity of a novel pathogen with other respiratory pathogens that can cause similar clinical presentations.
“Fewer than 0.01% of specimens tested positive for both SARS-CoV-2 and an eCoV,” he explained. “This suggested no significant cross-reactivity between SARS-CoV-2 and eCoVs on either test and provided a SARS-CoV-2 negative predictive value over 99% from an eCoV-positive specimen … The data we collected was highly compelling and the conclusion was that there was no coinfection.”
Chairing the two days of presentations at this weeks’ Canadian Diagnostic Executive Forum was Kevin D. Orr (above), Senior Director of Hospital Business at In-Common Laboratories. He also served on the program for this national conference serving clinical laboratories, anatomic pathology labs, and in vitro diagnostics (IVD) companies throughout Canada. This was the first gathering of this conference since 2019. Attendees were enthusiastic about the future of medical laboratory services in Canada, despite lab staffing shortages and rising costs due to inflation. (Photo copyright The Dark Report.)
Clinical Laboratory Regionalization in Quebec
One of Canada’s largest projects to regionalize and harmonize clinical laboratory services is proceeding in Quebec. Leading this effort is Ralph Dadoun, PhD, Project Director for OPTILAB Montreal, which is part of the Ministry of Health and Social Services in Quebec. The ambitious goal for this project is to move the 123 clinical laboratories within the province into 12 clusters. Initial planning was begun in 2013, so this project is in its ninth year of implementation.
During his presentation, Dadoun explained that the work underway in the 12 clusters involves creating common factors in these categories:
Implementation consistent with and respecting ISO-15189 criteria.
Another notable achievement in Quebec is the progress made to implement a common laboratory information system (LIS) within all 12 clusters. The first three laboratory clusters are undergoing their LIS conversions to the same platform during the next 180 days. The expectation is that use of a common LIS across all clinical laboratory sites in Quebec will unlock benefits in a wide spectrum of lab activities and work processes.
The 2022 CDEF featured speakers from most of the provinces. The common themes in these presentations were the shortage of lab personnel across all technical positions, disruptions in lab supplies, and the need to support the usual spectrum of lab testing services even as lab budgets are getting squeezed.
At the same time, there was plenty of optimism. Presentations involving adoption of digital pathology, advances in early disease detection made possible by new diagnostic technologies, and the expansion of precision medicine showed that clinical laboratories in Canada are gaining tools that will allow them to contribute to better patient care while helping reduce the downstream costs of care.
The Canadian Diagnostics Executive Forum is organized by a team from In-Common Laboratories in North York, Toronto, Ontario. Founded in 1967, it is a private, not-for-profit company that works with public hospitals and laboratory medicine providers. Information about CDEF can be found at its website, where several of this year’s presentations will be available for viewing.