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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Medical Genome Reference Bank Uses Whole-Genome Sequencing to Add 4,000 Healthy Older Adults to Its Huge Database

The resulting genomic dataset may provide useful diagnostic insights that can be used by clinical laboratory and pathology professionals to learn how and why some people age with good health

Why do some seniors age in good health and other seniors suffer with multiple chronic conditions? A new genetic database is using whole-genomic sequencing (WGS) to answer that question in ways that may benefit medical laboratories.

Because of the rapid aging of populations in the United States and other developed nations throughout the world, there is keen interest in how to keep seniors healthy. In fact, developing effective lab testing services in support of improved senior health is one of the big opportunities for both clinical laboratories and anatomic pathology groups.

Until recent years, most clinical pathologists dealt primarily with lab tests that used specimens such as blood and urine. However, genetics researchers are using WGS to discover new causes for many chronic illnesses. And the tools these researchers are developing offer pathologists and clinical laboratories powerful new ways to help doctors diagnose disease.

One genetics study involved a collaboration between the Garvan Institute of Medical Research at the University of New South Wales (UNSW) and Monash University. The research, launched in 2012, resulted in a database called the Medical Genome Reference Bank (MGRB).

Through the use of WGS, the MGRB now features a huge database of thousands of healthy elderly people. The data it contains may enable pathology scientists to learn, from a genetic standpoint, why some people age healthfully while others do not.

The researchers published their work titled, “The Medical Genome Reference Bank: A Whole-Genome Data Resource of 4,000 Healthy Elderly Individuals. Rationale and Cohort Design,” in the European Journal of Human Genetics.

Finding New Applications for Genetic Data

According to the UNSW published study, “The MGRB is comprised of individuals consented through the biobank programs of two contributing studies … Each sample is from an individual who has lived to [greater than or equal to] 70 years with no reported history or current diagnosis of cardiovascular disease, dementia, or cancer, as confirmed by the participating studies at recent follow-up study visits.”

The researchers noted in their paper, “Aged and healthy populations are more likely to be selectively depleted of pathogenic alleles, and therefore particularly suitable as a reference population for the major diseases of clinical and public health importance.”

The MGRB plans to make its database openly accessible to the international research community through its website once all 4,000 samples have been sequenced. Currently, about 3,000 of the samples have been analyzed, as noted on the Garvan website, which is tracking the MGRB’s progress.

“The Medical Genome Reference Bank can tell us much about what it means to grow old but remain well, and is a powerful tool to help us deconstruct the genetics of common diseases,” said David Thomas, PhD (above), an NHMRC Principal Research Fellow, Director of The Kinghorn Cancer Center, and Head of the Cancer Division of the Garvan Institute in New South Wales, AU, in a statement reported by GenomeWeb. (Photo copyright: South West Sydney Research.)

Personal Genetic Data in Precision Medicine

“The integration of genomic knowledge and technologies into healthcare is revolutionizing the way we approach clinical and public health practice,” Caron M. Molster, et al, noted in, “The Evolution of Public Health Genomics: Exploring Its Past, Present, and Future,” published in Frontiers in Public Health. Molster is Manager at the Health Department Western Australia in Perth, and lead author of the paper.

“Public health genomics has evolved to responsibly integrate advancements in genomics into the fields of personalized medicine and public health,” the researchers wrote.

The 100,000 Genomes Project in the United Kingdom is sequencing the genomes of people who have rare diseases and their families. Researchers all over the world are collecting genomic data with plans to use it in different ways, and on various chronic disease populations, in pursuit of precision medicine goals.

Molster and her co-authors noted the comparable development of genetic sequencing and precision medicine in their paper.

“Parallel to the developments in precision medicine has been the advancement of technologies that enable the production, aggregation, analysis, and dissemination of extremely large volumes of individual- and population-level data on genes, environment, behavior, and other social and economic determinants of health. These data have proven useful in finding new correlations, patterns and trends, particularly those involving complex interactions, in relation to diseases, pathogens, exposures, behaviors, susceptibility (risk), and health outcomes in populations,” they wrote.

According to Paul Lacaze, PhD, Head of the Public Health Genomics Program at Monash University, one of the challenges in interpreting whole-genome data in order to diagnose disease is “discriminating rare candidate disease-causing variants from the large numbers of benign variants unique to each individual. Reference populations are powerful filters,” he noted in the MGRB paper.

The MGRB database provides just such a powerful reference population, giving researchers who are studying specific diseases a tool for comparison.

Other Studies into Heathy Aging

Other initiatives to create datasets of genome information for specific populations also are underway. The Scripps Translational Science Institute (STSI) in La Jolla, Calif., has been studying healthy aging since 2007. That’s when STSI launched the Wellderly Study, according to a news release. As of 2016, they had sequenced the genomes of 600 study participants, as well as 511 samples for comparison from a study being conducted separately by the Inova Translational Medicine Institute, a paper in Nature noted.

Another effort being conducted in China involves a database called PGG.Population. These researchers seek to “create a comprehensive depository of geographic and ethnic variation of human genome, as well as a platform bringing influence on future practitioners of medicine and clinical investigators,” according to their 2018 paper published in Nucleic Acids Research.

In this case, rather than identifying common genomic variants among a specific population, such as the healthy elderly, the researchers are working to understand how genetic variations are distributed among specific populations. “The PGG.Population database documents 7,122 genomes representing 356 global populations from 107 countries and provides essential information for researchers to understand human genomic diversity and genetic ancestry,” wrote the researchers.

Each of these disparate datasets represents paths of investigation that could lead to a better understanding of personal and public health. As technologies continue to develop that enable scientists to sift through the massive amount of WGS data being generated, a clearer picture of what healthy aging at the genetic level looks like will likely emerge.

Precision medicine is leading to precision public health, and clinical pathology laboratories are important parts of the public health puzzle.

—Dava Stewart

Related Information:

Genome Sequencing Data from Thousands of Healthy Elderly People Now Available  

The Medical Genome Reference Bank: A Whole-Genome Data Resource of 4000 Healthy Elderly Individuals. Rationale and Cohort Design

The Evolution of Public Health Genomics: Exploring Its Past, Present, and Future

Wellderly Study Suggests Link Between Genes That Protect Against Cognitive Decline and Overall Healthy Aging

Harvard and Beth Israel Deaconess Researchers Use Machine Learning Software Plus Human Intelligence to Improve Accuracy and Speed of Cancer Diagnoses

Machine learning software may help pathologists make earlier and more accurate diagnoses

In Boston, two major academic centers are teaming up to apply big data and machine learning to the problem of diagnosing cancers earlier and with more accuracy. It is research that might have major implications for the anatomic pathology profession.

A collaborative effort between teams at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) has resulted in an innovation that could result in more accurate diagnoses in the pathology laboratory. The teams have been working on a machine learning software program that will eventually function as an artificial intelligence (AI) to improve the accuracy of diagnostics. They hope to someday build AI-powered computer systems that can accurately and quickly interpret pathology images. (more…)

Not a Surprise for Pathologists: Study Determines Doctors Fail to Follow Up on as Many as 60% Clinical Laboratory Test Results

Researchers looked at how physicians in ambulatory settings followed up on the results of medical laboratory tests

Studies performed in the United States show that, for ambulatory patients, doctors fail to follow up on as many as two-thirds of medical laboratory test results and up to one-third of radiology reports! A recent review of 19 of these studies also showed that these failures resulted in serious lapses in patient care.

It was researchers at the University of New South Wales (UNSW) who undertook a systematic review of evidence of failure to follow up on diagnostic test results and how this impacted ambulatory patients. The review was the first of its kind, internationally, according to a story published on UNSW’s Australian Institute of Health Innovation (AIHI) website.

Failure to Follow Up on Results of Clinical Laboratory Tests

“Failure to follow-up [on medical laboratory and radiology] test results for patients is a critical safety issue which requires urgent attention,” declared lead researcher Joanne L. Callen, Ph.D., in a story published by Medical Xpress. “Without knowledge of the size and effect of the problem, many clinicians may underestimate its extent and consequences.” Callen is an Associate Professor at UNSW and works as a Senior Research Fellow in the Centre for Health Systems and Safety ResearchThe Journal of General Internal Medicine published the review article.

The research team examined 19 studies that were conducted in the United States, where most of the research is being done, according to Callen. The U.S. studies quantified the extent of the failure to follow up clinical laboratory and radiology tests. Settings included ambulatory patients attending outpatient clinics, academic medical centers, community health centers, and primary care practices.

The investigators found that doctors in the United States fail to follow up as many as 62% of clinical pathology laboratory tests and up to 35% of radiology reports. This means that they are missing critical diagnoses. In turn, this causes delays in treatments for many conditions, including cancer, the AIHI story stated.

Researchers at the University of New South Wales (UNSW) found that doctors fail to follow up as many as 62% of clinical laboratory tests and up to 35% of radiology reports that they ordered for their patients. The UNSW study team reviewed 19 studies involving ambulatory patients conducted in the United States, where most of the research on this subject has been conducted. (Photo by

Researchers at the University of New South Wales (UNSW) found that doctors fail to follow up as many as 62% of clinical laboratory tests and up to 35% of radiology reports that they ordered for their patients. The UNSW study team reviewed 19 studies involving ambulatory patients conducted in the United States, where most of the research on this subject has been conducted. (Photo by

The 19 studies included in the review reported a wide variation in the extent of diagnostic tests not followed up by the ordering physician. For medical laboratory tests, results varied from 6.8% (79/1163) to 62% (125/202). For radiology, the results varied from 1.0% (4/395) to 35.7% (45/126), according to the review abstract.

Studies Showed Improved Test Follow Up With Use of Electronic Systems

The practices and processes currently used are varied and unsystematic, the review authors wrote. They noted that most primary care practices are not using electronic health record (EHR) systems. Further, they stated that most are communicating with multiple clinical laboratories that are often not electronically connected.

“Quantitative evidence of the effectiveness of electronic test management systems was limited,” the authors observed in the abstract. However, they found that “there was a general trend towards improved test follow up when electronic systems were used.”

The researchers also pointed out that feedback on medical errors is essential in order to counteract overconfidence in decision making vis-à-vis diagnostic accuracy. “Without knowledge of the size of the problem, many clinicians may underestimate its extent and therefore fail to take any action to improve the process,” they stated in the abstract.

The researchers concluded that solutions to the problem of missed diagnostic test results require a multi-faceted approach. Their recommendations included addressing the following areas:

  • policies relating to responsibility, timing and process of notification;
  • integrated IT and communications technologies;
  • consideration of the multidisciplinary nature of the process; and,
  • the role of the patient as a possible safety net against error.

Pathologists Can Read the Original UNSW Paper

Pathologists and clinical laboratory managers may want to access the original paper published by Callen and her colleagues. The paper’s statistics and findings may be useful in educating physicians about why failure to follow up on medical laboratory test results is a bigger problem than currently acknowledged.

In fact, publication of this study creates another opportunity for medical laboratories to add value to clinicians by helping them avoid missing key lab test results that might be overlooked. Such assistance is particularly important at a time when an important component of physician reimbursement is based on improvement in patient outcomes.

—Pamela Scherer McLeod

Related Information:

Doctors failing to follow-up test results

Failure to Follow-Up Test Results for Ambulatory Patients: A Systematic Review

Calls for patients to take charge of medical tests

Medical test results – why no news doesn’t mean good news