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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Virginia Commonwealth University Study Determines 40% of Americans Have Liver Disease

Clinical laboratories and anatomic pathology groups should prepare for a marked increase in orders for liver disease testing

New research from Virginia Commonwealth University’s Institute for Liver Disease and Metabolic Health in Richmond shows that four out of every 10 Americans has fatty liver disease of some type, according to a news release. Forty percent of Americans is an astonishing number! The study’s findings will almost certainly lead to clinical laboratories performing more testing in support of diagnosis, treatment decision making, and patient monitoring for liver disease than currently ordered by physicians.

Hepatologist Juan Pablo Arab, MD, director of alcohol sciences at Virginia Commonwealth University (VCU), led the team that conducted the research. He noted that the driving force behind the numbers is obesity and type two diabetes.

The researchers based their study on data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, which recorded the health of more than 5,000 individuals from 2017 to 2018, Newsmax reported.

“By 2018, federal data showed that 42% of adults had some form of fatty liver disease—higher than prior estimates,” Arab’s team told Newsmax, adding that “Hispanic adults were at especially high risk … with nearly half (47%) affected.”

The scientists published their findings in Nature Communications Medicine titled, “Disparities in Steatosis Prevalence in the United States by Race or Ethnicity according to the 2023 Criteria.”

“This study highlights a significant health issue that affects a large portion of the US population, and it shows that certain groups are at a higher risk. We hope these findings will guide more targeted health interventions to reduce the burden of liver disease, especially in high-risk communities,” said Juan Pablo Arab, MD (above), hepatologist with VCU’s Institute for Liver Disease and Metabolic Health, director of alcohol sciences, and lead researcher in the VCU study, in a VCU news release. These insights can be expected to lead to guidelines calling for more clinical laboratory testing associated with the diagnosis of fatty liver disease. (Photo copyright: Virginia Commonwealth University.)

Clinical Laboratory Testing

The VCU researchers found that metabolic dysfunction-associated steatotic liver disease (MASLD), also known as nonalcoholic fatty liver disease (NAFLD), was primarily brought on by obesity and type 2 diabetes.

“Groups at greater risk for MASLD include men, adults older than 40, individuals with health insurance, those with higher body mass index, and people with other health issues like diabetes, high blood pressure, high triglycerides, and low levels of good cholesterol. Interestingly, the study found that black individuals had the lowest risk of developing MASLD compared with other groups,” the VCU news release notes.

Fatty liver disease can also be caused by excessive alcohol consumption (called alcohol-associated liver disease or ALD) or a combination of both metabolic dysfunction and moderate-to-high alcohol intake, which is called MetALD, Newsmax reported.

“Although MASLD was the most common type of liver disease found in this study, the researchers also uncovered substantial rates of MetALD and alcohol-associated liver disease. For MetALD, the study showed that men and individuals with a higher BMI [body mass index] were at a greater risk, and Asians were at lower risk. Surprisingly, the only factor that appeared to lower the risk of ALD was having health insurance, though the reasons for this are not clear,” according to the VCU news release.

On its website, Mayo Clinic notes that NAFLD is often symptomless, and that doctors typically depend on routine clinical laboratory blood test results to reach a diagnosis. Additional testing helps determine whether higher than normal liver enzymes are actually from fatty liver disease or some other condition.

Medical laboratories play a key role in facilitating the final diagnoses. According to Mayo Clinic, blood tests to identify liver disease include:

Medical imaging could also be required to reach a diagnosis, beginning with an abdominal ultrasound, Mayo Clinic added. Additionally, more precise tests may be ordered to determine the stiffness of the liver and likelihood of scarring or fibrosis. Those modalities include:

Labs will often perform these tests on the same patient multiple times as the patient’s lifestyle changes. A liver biopsy may also be required to determine severity of damage, Mayo Clinic added.

Increase in Testing

Fatty liver disease at its most severe can lead to acute liver failure and fatal kidney complications, the American Liver Foundation (ALF) reported. If symptoms appear, a patient may experience “fatigue, weakness, weight loss, loss of appetite, nausea,

abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid buildup and swelling of the legs (edema) and abdomen (ascites), and mental confusion,” the ALF added.

As more healthcare providers focus their attention on diagnosing and treating this potentially deadly disease, clinical laboratories and anatomical pathology groups will likely see an uptick in tests ordered by doctors moving from initial diagnoses to more detailed testing and eventually to treatment follow ups.

—Kristin Althea O’Connor

Related Information:

Fatty Liver Disease Now Affects Four in 10 US Adults

More than 40% of US Adults Have Liver Disease, with Higher Risk among Hispanics, New Study Finds

Disparities in Steatosis Prevalence in the United States by Race or Ethnicity According to the 2023 Criteria

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Nonalcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD)

Washington University Researchers Uses Medical Laboratory Test Results and Big Data to Find Accelerated Aging and Risk of Early Cancer in Young Adults

Study shows that computer analysis of clinical laboratory test results has improved greatly in recent years

Studies using “big data” continue to show how combining different types of healthcare information can generate insights not available with smaller datasets. In this case, researchers at Washington University School of Medicine (WashU Medicine), St. Louis, Mo., determined that—by using the results from nine different types of clinical laboratory tests—they could correlate those test results to younger people who had “aged faster” and had developed cancer earlier than usual, according to CNN.

“Accumulating evidence suggests that the younger generations may be aging more swiftly than anticipated, likely due to earlier exposure to various risk factors and environmental insults. However, the impact of accelerated aging on early-onset cancer development remains unclear,” said Ruiyi Tian, PhD candidate at WashU Medicine’s Yin Cao Lab in an American Association for Cancer Research (AACR) news release.

The scientists presented their findings, which have not yet been published, at the AACR’s annual meeting held in April. Tian and the other researchers “hypothesized that increased biological age, indicative of accelerated aging, may contribute to the development of early-onset cancers, often defined as cancers diagnosed in adults younger than 55 years. In contrast to chronological age—which measures how long a person has been alive—biological age refers to the condition of a person’s body and physiological processes and is considered modifiable,” AACR noted in a news release.

“We all know cancer is an aging disease. However, it is really coming to a younger population. So, whether we can use the well-developed concept of biological aging to apply that to the younger generation is a really untouched area,” Yin Cao, ScD MPH (above), associate professor of surgery and associate professor of medicine at Washington University School of Medicine in St. Louis, and senior author of the study, told CNN. Analysis of clinical laboratory test results using computer algorithms continues to show value for new research into deadly diseases. (Photo copyright: Washington University.)

Lab Tests Share Insights about Aging

To acquire the data they needed for their research, the WashU Medicine scientists turned to the UK Biobank, a biomedical and research resource with genetic and health information on half a million UK residents.

The researchers reviewed the medical records of 148,724 biobank participants, age 37 to 54, focusing on nine blood-based biomarkers that “have been shown to correlate with biological age,” CNN reported. Those biomarkers are:

According to CNN, the researchers “plugged” the nine values into an algorithm called PhenoAge. Using the algorithm they compared the biological ages with each person’s actual chronological age to determine “accelerated aging.” They then consulted cancer registries to capture data on those in the study who were diagnosed with cancer before age 55. They found 3,200 cases.

Young Adults Aging Faster than Earlier Generations

According to the AACR news release, the WashU Medicine study found that:

  • “Individuals born in or after 1965 had a 17% higher likelihood of accelerated aging than those born between 1950 and 1954.
  • “Each standard deviation increase in accelerated aging was associated with a 42% increased risk of early-onset lung cancer, a 22% increased risk of early-onset gastrointestinal cancer, and a 36% increased risk of early-onset uterine cancer.
  • “Accelerated aging did not significantly impact the risk of late-onset lung cancer (defined here as cancer diagnosed after age 55), but it was associated with a 16% and 23% increased risk of late-onset gastrointestinal and uterine cancers, respectively.”

“We speculate that common pathways, such as chronic inflammation and cellular senescence, may link accelerated aging to the development of early-onset cancers,” the study’s principal investigator Yin Cao, ScD, MPH, associate professor of surgery and associate professor of medicine at WashU Medicine, told The Hill.

“Historically, both cancer and aging have been viewed primarily as concerns for older populations. The realization that cancer, and now aging, are becoming significant issues for younger demographics over the past decades was unexpected,” Tian told Fox News.

More Screenings, Further Analysis

The study’s results may suggest a change in clinical laboratory screenings for younger people.

“We see cancers earlier all the time now, and nobody knows why. The subset in the population that has accelerated aging may need screening more often or earlier,” Emanuela Taioli, MD, PhD, professor of population health and science and of thoracic surgery, and director of the Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, told Health.

In future studies, WashU Medicine scientists may aim to include groups of greater diversity and explore why people are aging faster and have risk of early-onset cancers. 

“There is room to improve using better technologies. Looking at the bigger picture, the aging concept can be applied to younger people to include cancers, cardiovascular disease, and diabetes,” Cao told Discover Magazine.

While more research is needed, use of the UK’s Biobank of healthcare data—including clinical laboratory test results—enabled the WashU Medicine researchers to determine that accelerated aging among young adults is happening with some regularity. This shows that capabilities in computer analysis are gaining more refined capabilities and are able to tease out insights impossible to achieve with earlier generations of analytical software.

These findings should inspire clinical laboratory professionals and pathologists to look for opportunities to collaborate in healthcare big data projects involving their patients and the communities they serve.

—Donna Marie Pocius

Related Information:

Accelerated Aging May Increase the Risk of Early-onset Cancers in Younger Generations

Accelerated Aging Linked to Cancer Risk in Younger Adults, Research Shows

An Epigenetic Biomarker of Aging for Lifespan and Health Span in Aging

Accelerated Aging May be a Cause of Increased Cancers in People under 55

Cancer Rates Rising in Young People Due to “Accelerated Aging,” New Study Finds

Research Shows Accelerated Aging Linked to Increased Cancer Risk in Younger Adults

Rate of Biological Aging is Accelerating in Young People, Leading to Medical Issues

Woman Performs Do-it-yourself Fecal Transplant to Relieve Symptoms of IBS, Gets Donor’s Acne

Clinical laboratory scientists and microbiologists could play a role in helping doctors explain to patients the potential dangers of do-it-yourself medical treatments

Be careful what you wish for when you perform do-it-yourself (DIY) medical treatments. That’s the lesson learned by a woman who was seeking relief for irritable bowel syndrome (IBS). When college student Daniell Koepke did her own fecal transplant using poop from her brother and her boyfriend as donors her IBS symptoms improved, but she began to experience medical conditions that afflicted both fecal donors.

“It’s possible that the bacteria in the stool can influence inflammation in the recipient’s body, by affecting their metabolism and activating their immune response,” microbial ecologist Jack Gilbert, PhD, Professor and Associate Vice Chancellor at University of California San Diego (UC San Diego) told Business Insider. “This would cause shifts in their hormonal activity, which could promote the bacteria that can cause acne on the skin. We nearly all have this bacterium on skin, but it is often dormant,” he added.

A Fecal Microbiota Transplant (FMT) is a procedure where stool from a healthy donor is transplanted into the microbiome of a patient plagued by a certain medical condition.

Our guts are home to trillions of microorganisms (aka, microbes), known as the gut microbiota, that serve many important functions in the body. The microbiome is a delicate ecosystem which can be pushed out of balance when advantageous microbes are outnumbered by unfavorable ones. An FMT is an uncomplicated and powerful method of repopulating the microbiome with beneficial microbes.   

“With fecal microbiome transplants there is really compelling evidence, but the science is still developing. We’re still working on if it actually has benefits for wider populations and if the benefit is long-lasting,” said Gilbert in a Netflix documentary titled, “Hack Your Health: The Secrets of Your Gut.”

“The microbial community inside our gut can have surprising influences on different parts of our body,” microbial ecologist Jack Gilbert, PhD (above), of the Gilbert Lab at University of California San Diego told Business Insider. “Stools are screened before clinical FMTs, and anything that could cause major problems, such as certain pathogens, would be detected. When you do this at home, you don’t get that kind of screening.” Doctors and clinical laboratories screening patients for IBS understand the dangers of DIY medical treatments. (Photo copyright: University of California San Diego.)

Changing Poop Donors

When Koepke began experiencing symptoms of IBS including indigestion, stabbing pains from trapped gas and severe constipation, she initially turned to physicians for help.

In the Netflix documentary, Koepke stated that she was being prescribed antibiotics “like candy.” Over the course of five years, she completed six rounds of antibiotics per year, but to no avail.

She also changed her diet, removing foods that were making her symptoms worse. This caused her to lose weight and she eventually reached a point where she could only eat 10 to 15 foods. 

“It’s really hard for me to remember what it was like to eat food before it became associated with anxiety and pain and discomfort,” she said.

In an attempt to relieve her IBS symptoms, Koepke made her own homemade fecal transplant pills using donated stool from her brother. After taking them her IBS symptoms subsided and she slowly gained weight. But she developed hormonal acne just like her brother. 

Koepke then changed donors, using her boyfriend’s poop to make new fecal transplant pills. After she took the new pills, her acne dissipated but she developed depression, just like her boyfriend. 

“Over time, I realized my depression was worse than it’s ever been in my life,” Koepke stated in the documentary.

She believes the microbes that were contributing to her boyfriend’s depression were also transplanted into her via the fecal transplant pills. When she reverted to using her brother’s poop, her depression abated within a week.

Gilbert told Business Insider his research illustrates that people who suffer from depression are lacking certain bacteria in their gut microbiome.

“She may have had the ‘anti-depressant’ bacteria in her gut, but when she swapped her microbiome with his, her anti-depressant bacteria got wiped out,” he said.

FDA Approves FMT Therapy for Certain Conditions

Typically, the fecal material for an FMT procedure performed by a doctor comes from fecal donors who have been rigorously screened for infections and diseases. The donations are mixed with a sterile saline solution and filtered which produces a liquid solution. That solution is then administered to a recipient or frozen for later use. 

Fecal transplant methods include:

On November 30, 2022, the US Food and Drug Administration (FDA) approved the first FMT therapy, called Rebyota, for the prevention of Clostridioides difficile (C. diff.) in adults whose symptoms do not respond to antibiotic therapies. Rebyota is a single-dose treatment that is administered rectally into the gut microbiome at a doctor’s office. 

Then, in April of 2023, the FDA approved the use of a medicine called Vowst, which is the first oral FMT approved by the FDA.

According to the Cleveland Clinic, scientists are exploring the possibility that fecal transplants may be used as a possible treatment for many health conditions, including:

Doctors and clinical laboratories know that do-it-yourself medicine is typically not a good idea for obvious reasons. Patients seldom appreciate all the implications of the symptoms of an illness, nor do they fully understand the potentially dangerous consequences of self-treatment. Scientists are still researching the benefits of fecal microbiota transplants and hope to discover more uses for this treatment. 

—JP Schlingman

Related Information:

A Woman Gave Herself Poop Transplants Using Her Brother’s Feces to Treat Debilitating IBS. Then She Started Getting Acne Just Like Him.

FDA Approves First Orally Administered Fecal Microbiota Product for the Prevention of Recurrence of Clostridioides Difficile Infection

FDA Approves First FMT Therapy and Issues Guidance

Everything You Want to Know about Irritable Bowel Syndrome (IBS)

Stanford University Scientists Discover New Lifeform Residing in Human Microbiome

Microbiome Firm Raises $86.5 Million and Inks Deal to Sell Consumer Test Kits in 200 CVS Pharmacies

Researchers Find Health of Human Microbiome Greatly Influenced by Foods We Eat

Scientists at UT Health San Antonio Discover New Biomarker for Diabetic Kidney Disease

Biomarker may lead to clinical laboratory testing that enables clinical pathologists and urologists to diagnose risk for diabetic kidney failure years before it occurs

Clinical laboratories working with nephrologists and urologists to diagnose patients experiencing urinary system difficulties know that albumin (excessive protein found in the urine) is a common biomarker used in clinical laboratory testing for kidney disease. But patients with diabetes generally have low protein in their urine due to that disease. Thus, it is difficult to diagnose early stage kidney failure in diabetic patients.

But now, researchers at the University of Texas Health Science Center at San Antonio (UT Health San Antonio) have discovered a biomarker called adenine (also found in the urine) which, they say, offers the ability to diagnose diabetic patients at risk of kidney failure significantly earlier than other biomarkers.

A UT Health San Antonio news release states, “Urine levels of adenine, a metabolite produced in the kidney, are predictive and a causative biomarker of looming progressive kidney failure in patients with diabetes, a finding that could lead to earlier diagnosis and intervention.”

The study’s senior author Kumar Sharma, MD, professor and Chief of Nephrology at UT Health San Antonio, said, “The finding paves the way for clinic testing to determine—five to 10 years before kidney failure—that a patient is at risk.”

The UT Health scientists published their research in the Journal of Clinical Investigation (JCI) titled, “Endogenous Adenine Mediates Kidney Injury in Diabetic Models and Predicts Diabetic Kidney Disease in Patients.”

“The study is remarkable as it could pave the way to precision medicine for diabetic kidney disease at an early stage of the disease,” said study lead Kumar Sharma, MD (above), professor and Chief of Nephrology at UT Health San Antonio, in a news release. This would be a boon to clinical laboratories and pathology groups that work with urologists to diagnose and treat diabetic patients who are at-risk for kidney failure. (Photo copyright: UT Health San Antonio.)

Completing the UT Health Study

Sharma and his team worked for five years to discover that the adenine molecule was damaging kidney tissue, News4SA reported. The research required the team to develop new methods for viewing small molecules known as metabolites.

“UT Health San Antonio is one of few centers in the US perfecting a technique called spatial metabolomics on kidney biopsies from human patients,” the news release notes. The kidney biopsies were obtained through the Kidney Precision Medicine Project (KPMP) and were gathered from various US academic centers.

“It’s a very difficult technique, and it took us several years to develop a method where we combine high resolution of the geography of the kidney with mass spectrometry analysis to look at the metabolites,” Sharma said.

Testing by the UT Health team unearthed “endogenous adenine around scarred blood vessels in the kidney and around tubular-shaped kidney cells that were being destroyed. Endogenous substances are those that naturally occur in the body,” the news release notes.

Findings Could Affect Diabetic Care

UT Health San Diego’s study findings could allow for early intervention and change the way diabetes care is managed, Sharma said.

“The study results are significant because until now, the most important marker for kidney disease has been protein (or albumin) in the urine. Up to half of diabetes patients who develop kidney failure never have much protein in their urine. As 90% of patients with diabetes (more than 37 million patients in the US) remain at increased risk despite low levels of albumin in their urine, this study has widespread consequences. It is the first study to identify these patients at an early stage by measuring this new causative marker in the urine,” the UT Health news release states.

“We’re hoping that by identifying patients early in their course, and with new therapies targeting adenine and kidney scarring, we can block kidney disease or extend the life of the kidney much longer,” Sharma said.

Getting Ahead of Kidney Disease

Though many patients recognize their risk for kidney disease, those who do not have protein in their urine may not take the risk seriously enough, Sharma noted.

“They could be feeling a false sense of security that there is no kidney disease occurring in their body, but in fact, in many cases it is progressing, and they often don’t find out until the kidney disease is pretty far advanced. And at that time, it is much harder to protect the kidneys and prevent dialysis,” he said in the new release.

“Once a patient needs dialysis, he or she must have a fistula or catheter placed and go on a dialysis machine three times a week, four hours at a time to clean the blood,” the news release states.

“The death rate is very high, especially in patients with diabetes,” Sharma added. “There is about 40% mortality within five years in patients with diabetes and kidney failure.”

Though measuring adenine in urine is a challenge, Sharma and his team developed a method that can be performed at UT Health San Antonio on at-risk patients with a doctor’s order. The test results go back to the patient’s doctor.

“The test is being approved for clinical use and right now it is an experimental test, but we expect it to be available for all patients in the near future.” Sharma told News4SA.

“What we’re hoping is that by identifying patients early in their course, and with new therapies targeting adenine and kidney scarring, we can block kidney disease or extend the life of the kidney much longer,” Sharma said in the news release.

And so, thanks to the UT Health researchers, pathologists and clinical laboratories may soon see a new diagnostic test biomarker that will help urologists identify diabetic patients at-risk for kidney failure years earlier than previously possible.

—Kristin Althea O’Connor

Related Information:

Endogenous Adenine Mediates Kidney Injury in Diabetic Models and Predicts Diabetic Kidney Disease in Patients

Metabolite in Urine Predicts Diabetic Kidney Failure 5-10 Years Early; Oral Therapeutic Drug Shows Promise in Mice

Revolutionizing Diabetes Care: UT Health San Antonio’s Breakthrough in Predicting Kidney Failure

UT Health San Antonio Discovers Molecule Predicting Kidney Failure in Diabetics

Cambridge Researchers in UK Develop ‘Unknome Database’ That Ranks Proteins by How Little is Known about Their Functions

Scientists believe useful new clinical laboratory assays could be developed by better understanding the huge number of ‘poorly researched’ genes and the proteins they build

Researchers have added a new “-ome” to the long list of -omes. The new -ome is the “unknome.” This is significant for clinical laboratory managers because it is part of an investigative effort to better understand the substantial number of genes, and the proteins they build, that have been understudied and of which little is known about their full function.

Scientists at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge, England, believe these genes are important. They have created a database of thousands of unknown—or “unknome” as they cleverly dubbed them—proteins and genes that have been “poorly understood” and which are “unjustifiably neglected,” according to a paper the scientist published in the journal PLOS Biology titled, “Functional Unknomics: Systematic Screening of Conserved Genes of Unknown Function.”

The Unknome Database includes “thousands of understudied proteins encoded by genes in the human genome, whose existence is known but whose functions are mostly not,” according to a news release.

The database, which is available to the public and which can be customized by the user, “ranks proteins based on how little is known about them,” the PLOS Biology paper notes.

It should be of interest to pathologists and clinical laboratory scientists. The fruit of this research may identify additional biomarkers useful in diagnosis and for guiding decisions on how to treat patients.

Sean Munro, PhD

“These uncharacterized genes have not deserved their neglect,” said Sean Munro, PhD (above), MRC Laboratory of Molecular Biology in Cambridge, England, in a press release. “Our database provides a powerful, versatile and efficient platform to identify and select important genes of unknown function for analysis, thereby accelerating the closure of the gap in biological knowledge that the unknome represents.” Clinical laboratory scientists may find the Unknome Database intriguing and useful. (Photo copyright: Royal Society.)

Risk of Ignoring Understudied Proteins

Proteomics (the study of proteins) is a rapidly advancing area of clinical laboratory testing. As genetic scientists learn more about proteins and their functions, diagnostics companies use that information to develop new assays. But did you know that researchers tend to focus on only a small fraction of the total number of protein-coding DNA sequences contained in the human genome?

The study of proteomics is primarily interested in the part of the genome that “contains instructions for building proteins … [which] are essential for development, growth, and reproduction across the entire body,” according to Scientific American. These are all protein-coding genes.

Proteomics estimates that there are more than two million proteins in the human body, which are coded for 20,000 to 25,000 genes, according to All the Science.

To build their database, the MRC researchers ranked the “unknome” proteins by how little is known about their functions in cellular processes. When they tested the database, they found some of these less-researched proteins important to biological functions such as development and stress resistance. 

“The role of thousands of human proteins remains unclear and yet research tends to focus on those that are already well understood,” said Sean Munro, PhD, MRC Laboratory of Molecular Biology in Cambridge, England, in the news release. “To help address this we created an Unknome database that ranks proteins based on how little is known about them, and then performed functional screens on a selection of these mystery proteins to demonstrate how ignorance can drive biological discovery.”

Munro created the Unknome Database along with Matthew Freeman, PhD, Head of England’s Sir William Dunn School of Pathology, University of Oxford.

In the paper, they acknowledged the human genome encodes about 20,000 proteins, and that the application of transcriptomics and proteomics has “confirmed that most of these new proteins are expressed, and the function of many of them has been identified.

“However,” the authors added, “despite over 20 years of extensive effort, there are also many others that still have no known function.”

They also recognized limited resources for research and that a preference for “relative safety” and “well-established fields” are likely holding back discoveries.

The researchers note “significant” risks to continually ignoring unexplored proteins, which may have roles in cell processes, serve as targets for therapies, and be associated with diseases as well as being “eminently druggable,” Genetic Engineering News reported.

Setting up the Unknome Database

To develop the Unknome Database, the researchers first turned to what has already come to fruition. They gave each protein in the human genome a “knownness” score based on review of existing information about “function, conservation across species, subcellular localization, and other factors,” Interesting Engineering reported.

It turns out, 3,000 groups of proteins (805 with a human protein) scored zero, “showing there’s still much to learn within the human genome,” Science News stated, adding that the Unknome Database catalogues more than 13,000 protein groups and nearly two million proteins. 

The researchers then tested the database by using it to determine what could be learned about 260 “mystery” genes in humans that are also present in Drosophila (small fruit flies).

“We used the Unknome Database to select 260 genes that appeared both highly conserved and particularly poorly understood, and then applied functional assays in whole animals that would be impractical at genome-wide scale,” the researchers wrote in PLOS Biology.

“We initially selected all genes that had a knownness score of ≤1.0 and are conserved in both humans and flies, as well as being present in at least 80% of available metazoan genome sequences. … After testing for viability, the nonessential genes were then screened with a panel of quantitative assays designed to reveal potential roles in a wide range of biological functions,” they added.

“Our screen in whole organisms reveals that, despite several decades of extensive genetic screens in Drosophila, there are many genes with essential roles that have eluded characterization,” the researchers conclude.

Clinical Laboratory Testing Using the Unknome Database

Future use of the Unknome Database may involve CRISPR technology to explore functions of unknown genes, according to the PLOS Biology paper.

Munro told Science News the research team may work with other research efforts aimed at understanding “mysterious proteins,” such as the Understudied Proteins Initiative.

The Unknome Database’s ability to be customized by others means researchers can create their own “knownness” scores as it applies to their studies. Thus, the database could be a resource in studies of treatments or medications to fight diseases, Chemistry World noted.

According to a statement prepared for Healthcare Dive by SomaLogic, a Boulder, Colorado-based protein biomarker company, diagnostic tests that measure proteins can be applied to diseases and conditions such as:

In a study published in Science Translational Medicine, SomaLogic’s SomaScan assay was reportedly successful in predicting the likelihood within four years of myocardial infarction, heart failure, stroke, and even death.

“The 27-protein model has potential as a ‘universal’ surrogate end point for cardiovascular risk,” the researchers wrote in Science Translational Medicine.

Proteomics definitely has its place in clinical laboratory testing. The development of MRC-LMB’s Unknome Database will help researchers’ increase their knowledge about the functions of more proteins which should in turn lead to new diagnostic assays for labs.

—Donna Marie Pocius

Related Information:

Mapping the ‘Unknome’ May Reveal Critical Genes Scientists Have Ignored

How Many Proteins Exist?

Unknome: A Database of Human Genes We Know Almost Nothing About

Functional Unknomics: Systematic Screening of Conserved Genes of Unknown Function

Unknome Database Ranks Proteins Based on How Little is Known about Them

How a New Database of Human Genes Can Help Discover New Biology

The Unknome Catalogs Nearly Two Million Proteins. Many are Mysterious

Into the Unknome: Scientists at MRC LMB in Cambridge Create Database Ranking Human Proteins by How Little We know About Them

Scientists Hope to Illuminate Unknown Human Proteins with New Public Database

Proteomic Tests Empower Precision Medicine

A Proteomic Surrogate for Cardiovascular Outcomes That is Sensitive to Multiple Mechanisms of Change in Risk

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