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VA’s ‘Million Veterans Program’ Research Study Receives Its 100,000th Human Genome Sequence

With improved genetic sequencing comes larger human genome databases that could lead to new diagnostic and therapeutic biomarkers for clinical laboratories

As the COVID-19 pandemic grabbed headlines, the human genome database at the US Department of Veterans Affairs Million Veterans Program (MVP) quietly grew. Now, this wealth of genomic information—as well as data from other large-scale genomic and genetic collections—is expected to produce new biomarkers for clinical laboratory diagnostics and testing.

In December, cancer genomics company Personalis, Inc. (NASDAQ:PSNL) of Menlo Park, Calif., achieved a milestone and delivered its 100,000th whole human genome sequence to the MVP, according to a news release, which also states that Personalis is the sole sequencing provider to the MVP.

The VA’s MVP program, which started in 2011, has 850,000 enrolled veterans and is expected to eventually involve two million people. The VA’s aim is to explore the role genes, lifestyle, and military experience play in health and human illness, notes the VA’s MVP website.

Health conditions affecting veterans the MVP is researching include:

The VA has contracted with Personalis through September 2021, and has invested $175 million, Clinical OMICS reported. Personalis has earned approximately $14 million from the VA. That’s about 76% of the company’s revenue, according to 2nd quarter data, Clinical OMICS noted.

John West and wife Judy West of Personalis headshots
“The VA MVP is the largest whole genome sequencing project in the United States, and this is a significant milestone for both the program and for Personalis,” said John West (above with wife Judy), Founder and CEO of Personalis, in the news release. “Population-scale sequencing projects of this nature represent a cornerstone in our effort to accelerate the advancement of precision medicine across a wide range of disease areas,” he added. (Photo copyright: MIT Technology Review.)

Database of Veterans’ Genomes Used in Current Research

What has the VA gained from their investment so far? An MVP fact sheet states researchers are tapping MVP data for these and other veteran health-related studies: 

  • Gene variations associated with different tumor structures in patients with non-small-cell lung carcinoma.
  • Differentiating between prostate cancer tumors that require treatment and others that are slow-growing and not life-threatening.
  • How genetics drives obesity, diabetes, and heart disease.
  • How data in DNA translates into actual physiological changes within the body.
  • Gene variations and patients’ response to Warfarin.

NIH Research Program Studies Effects of Genetics on Health

Another research program, the National Institutes of Health’s All of Us study, recently began returning results to its participants who provided blood, urine, and/or saliva samples. The NIH aims to aid research into health outcomes influenced by genetics, environment, and lifestyle, explained a news release. The program, launched in 2018, has biological samples from more than 270,000 people with a goal of one million participants.

NIH’s All of Us program partners include:

Dr. Josh Denny CEO of NIH All of Us program headshot
“We’re changing the paradigm for research. Participants are our most important partners in this effort, and we know many of them are eager to get their genetic results and learn about the science they’re making possible,” said Josh Denny, MD, CEO of the NIH’s All of Us research program in the news release. Denny, a physician scientist, was Professor of Biomedical Informatics and Medicine, Director of the Center for Precision Medicine and Vice President for Personalized Medicine at Vanderbilt University Medical Center prior to joining the NIH. (Photo copyright: National Institutes of Health.)

Inclusive Data Could Aid Precision Medicine

The news release notes that more than 80% of biological samples in the All of Us database come from people in communities that have been under-represented in biomedical research.

“We need programs like All of Us to build diverse datasets so that research findings ultimately benefit everyone,” said Brad Ozenberger, PhD, All of Us Genomics Program Director, in the news release.

Precision medicine designed for specific healthcare populations is a goal of the All of Us program.

“[All of Us is] beneficial to all Americans, but actually beneficial to the African American race because a lot of research and a lot of medicines that we are taking advantage of today, [African Americans] were not part of the research,” Chris Crawford, All of US Research Study Navigator, told the Birmingham Times. “As [the All of Us study] goes forward and we get a big diverse group of people, it will help as far as making medicine and treatment that will be more precise for us,” he added.

Large Databases Could Advance Care

Genome sequencing technology continues to improve. It is faster, less complicated, and cheaper to sequence a whole human genome than ever before. And the resulting sequence is more accurate.

Thus, as human genome sequencing databases grow, researchers are deriving useful scientific insights from the data. This is relevant for clinical laboratories because the new insights from studying bigger databases of genomic information will produce new diagnostic and therapeutic biomarkers that can be the basis for new clinical laboratory tests as well as useful diagnostic assays for anatomic pathologists.

—Donna Marie Pocius

Related Information:

Personalis Announces Delivery of the 100,000th Genome to the U.S. Department of Veterans Affairs Million Veteran Program

VA Extends Personalis Contract for Million Veterans Project With $31M Task Order

Million Veteran Program Research Projects

All of Us Research Program Returns First Genetic Results to Participants

All of Us Research: Why Some Get Sick and Others Are in Great Health

February COVID-19 Superspreader Event in Boston Confirmed by Use of Genetic Sequencing as Next-Gen Sequencing Is Put to Novel Uses, including in Clinical Laboratories

Gene sequencing is enabling disease tracking in new ways that include retesting laboratory specimens from before the SARS-CoV-2 outbreak to determine when it arrived in the US

On February 26 of this year, nearly 200 executives and employees of neuroscience-biotechnology company Biogen gathered at the Boston Marriott Long Wharf hotel for their annual leadership conference. Unbeknownst to the attendees, by the end of the following day, dozens of them had been exposed to and become infected by SARS-CoV-2, the coronavirus that causes the COVID-19 illness.

Researchers now have hard evidence that attendees at this meeting returned to their communities and spread the infection. The findings of this study will be relevant to pathologists and clinical laboratory managers who are cooperating with health authorities in their communities to identify infected individuals and track the spread of the novel coronavirus.

This “superspreader” event has been closely investigated and has led to intriguing conclusions concerning the use of genetic sequencing to revealed vital information about the COVID-19 pandemic. Recent improvements in gene sequencing technology is giving scientists new ways to trace the spread of COVID-19 and other diseases, as well as a method for monitoring mutations and speeding research into various treatments and vaccines. 

Genetic Sequencing Traces an Outbreak

“With genetic data, a record of our poor decisions is being captured in a whole new way,” Bronwyn MacInnis, PhD, Director of Pathogen Genomic Surveillance at the Broad Institute of MIT and Harvard, told The Washington Post (WaPo) during its analysis of the COVID-19 superspreading event. MacInnis is one of many Broad Institute, Harvard, MIT, and state of Massachusetts scientists who co-authored a study that detailed the coronavirus’ spread across Boston, including from the Biogen conference.

Titled, “Phylogenetic Analysis of SARS-CoV-2 in the Boston Area Highlights the Role of Recurrent Importation and Superspreading Events,” the paper explains how the researchers “sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region” in order to investigate how the virus was introduced and spread through the area. They traced a specific mutation in the virus—“a simple switch of two letters in the virus’ 30,000-character genetic code,” WaPo reported.

What they discovered is both surprising and enlightening. According to WaPo’s report, at least 35 new cases of the virus were linked directly to the Biogen conference, and the same strain was discovered in outbreaks in two homeless shelters in Boston, where 122 people were infected. The variant tracked by the Boston researchers was found in roughly 30% of the cases that have been sequenced in the state, as well as in Alaska, Senegal, and Luxembourg.

“The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe. We studied two superspreading events covered by the data, events that led to very different outcomes because of the timing and populations involved. One produced rapid spread in a vulnerable population but little onward transmission, while the other was a major contributor to sustained community transmission,” the researchers noted in their study abstract.

“The same two events differed significantly in the number of new mutations seen, raising the possibility that SARS-CoV-2 superspreading might encompass disparate transmission dynamics. Our results highlight the failure of measures to prevent importation into [Massachusetts] early in the outbreak, underscore the role of superspreading in amplifying an outbreak in a major urban area, and lay a foundation for contact tracing informed by genetic data,” they concluded.

Anthony Fauci, MD
Some experts think humankind may be entering a period of increased pandemics. In their report published in Cell, titled, “Emerging Pandemic Diseases: How We Got to COVID-19,” Anthony Fauci, MD (above) Director of the National Institute of Allergy and Infectious Diseases (NIAID), and David Morens, MD, a senior associate professor at Johns Hopkins School of Public Health and Senior Advisor to Fauci, wrote, “One can conclude from this recent experience that we have entered a pandemic era. The causes of this new and dangerous situation are multifaceted, complex, and deserving of serious examination.” (Photo copyright: NIAID.)

Genetic Sequencing and Mutation Tracking

The use of genetic sequencing to trace the virus could inform measures to control the spread in new ways, but currently, only about 0.33% of cases in the United States are being sequenced, MacInnis told WaPo, and that not sequencing samples is “throwing away the crown jewels of what you really want to know.”

Another role that genetic sequencing is playing in this pandemic is in tracking viral mutations. One of the ways that pandemics worsen is when viruses mutate to become deadlier or more easily spread. Scientists are using genetic sequencing to monitor SARS-CoV-2 for such mutations.

A group of scientists at Texas A&M University led by Yue Xing, PhD, published a paper titled, “MicroGMT: A Mutation Tracker for SARS-CoV-2 and Other Microbial Genome Sequences,” which explains that “Although most mutations are expected to be selectively neural, it is important to monitor if SARS-CoV-2 will eventually evolve to be a stronger or weaker infectious agent as time goes on. Therefore, it is vital to track mutations from newly sequenced SARS-CoV-2 genome.”

Another group of researchers have identified such a mutation. “A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional, and municipal,” Bette Korber, PhD and her colleagues wrote in “Tracking Changes in SARS-CoV-2 Spike: Evidence That D614G Increases Infectivity of the COVID-19 Virus,” published in Cell. Korber is a Laboratory Fellow at Los Alamos National Laboratory and visiting faculty at Santa Fe Institute.

Korber’s findings are important because the mutation the scientists identified appears to have a fitness advantage. “Our data show that, over the course of one month, the variant carrying the D614G Spike mutation became the globally dominant form of SARS-CoV-2,” they wrote. Additionally, the study noted, people infected with the mutated variant appear to have a higher viral load in their upper respiratory tracts.

Genetic Sequencing, the Race for Treatments, Vaccines, and Managing Future Pandemics

A vaccine is the best hope for stopping a pandemic, but short of a vaccine, an effective clinical laboratory treatment is the next best thing. And as Dark Daily reported in “Advances in Gene Sequencing Technology Enable Scientists to Respond to the Novel Coronavirus Outbreak in Record Time with Medical Lab Tests, Therapies,” genetic sequencing is quickly becoming a critical tool to develop both.

If, as Fauci and Morens predict, future pandemics are likely, improvements in gene sequencing and analysis will become even more important for tracing, monitoring, and suppressing outbreaks. Clinical laboratory managers will want to watch this closely, as medical labs that process genetic sequencing will, no doubt, be part of that operation.

—Dava Stewart

Related Information:

Genetic Data Show How a Single Superspreading Event Sent Coronavirus Across Massachusetts and the Nation

How the Biogen Leadership Conference in Boston Spread the Coronavirus

How a Premier U.S. Drug Company Became a Virus ‘Super Spreader’

This Cambridge Drug Company Inadvertently Spread the Coronavirus. Now, It’s Creating A ‘Biobank’ To Hopefully Treat the Disease

Phylogenetic Analysis of SARS-CoV-2 in the Boston Area Highlights the Role of Recurrent Importation and Superspreading Events

MicroGMT: A Mutation Tracker for SARS-CoV-2 and Other Microbial Genome Sequences

Tracking Changes in SARS-CoV-2 Spike: Evidence That D614G Increases Infectivity of the COVID-19 Virus

The D614G Mutation in the SARS-CoV-2 Spike Protein Reduces S1 Shedding and Increases Infectivity

Emerging Pandemic Diseases: How We Got to COVID-19 Advances in Gene Sequencing Technology Enable Scientists to Respond to the Novel Coronavirus Outbreak in Record Time with Medical Lab Tests, Therapies

AdventHealth Gives 10,000 Floridians Free Genetic Tests, Sees Genomics as the Future of Precision Medicine

Many other healthcare systems also are partnering with private genetic testing companies to pursue research that drive precision medicine goals

It is certainly unusual when a major health network announces that it will give away free genetic tests to 10,000 of its patients as a way to lay the foundation to expand clinical services involving precision medicine. However, pathologists and clinical laboratory managers should consider this free genetic testing program to be the latest marketplace sign that acceptance of genetic medicine continues to move ahead.

Notably, it is community hospitals that are launching this new program linked to clinical laboratory research that uses genetic tests for specific, treatable conditions. The purpose of such genetic research is to identify patients who would benefit from test results that identify the best therapies for their specific conditions, a core goal of precision medicine.

The health system is AdventHealth of Orlando, Fla., which teamed up with Helix, a personal genomics company in San Mateo, Calif., to offer free DNA sequencing to 10,000 Floridians through its new AdventHealth Genomics and Personalized Health Program. A company news release states this is the “first large-scale DNA study in Florida,” and that it “aims to unlock the secret to a healthier life.”

The “WholeMe” genomic population health study screens people for familial hypercholesterolemia  (FH), a genetic disorder that can lead to high cholesterol and heart attacks in young adults if not identified and treated, according to the news release.

Clinical laboratory leaders will be interested in this initiative, as well other partnerships between healthcare systems and private genetic testing companies aimed at identifying and enrolling patients in research studies for disease treatment protocols and therapies. 

The Future of Precision Medicine

Modern Healthcare reported that data from the WholeMe DNA study, which was funded through donations to the AdventHealth Foundation, also will be used by the healthcare network for research beyond FH, as AdventHealth develops its genomics services. The project’s cost is estimated to reach $2 million.

“Genomics is the future of medicine, and the field is rapidly evolving. As we began our internal discussions about genomics and how to best incorporate it at AdventHealth, we knew research would play a strong role,” Wes Walker MD, Director, Genomics and Personalized Health, and Associate CMIO at AdventHealth, told Becker’s Hospital Review.

“We decided to focus on familial hypercholesterolemia screening initially because it’s a condition that is associated with life-threatening cardiovascular events,” he continued. “FH is treatable once identified and finding those who have the condition can lead to identifying other family members who are subsequently identified who never knew they had the disease.”

The AdventHealth Orlando website states that participants in the WholeMe study receive information stored in a confidential data repository that meets HIPAA security standards. The data covers ancestry and 22 other genetic traits, such as:

  • Asparagus Odor Detection
  • Bitter Taste
  • Caffeine Metabolism
  • Cilantro Taste Aversion
  • Circadian Rhythm
  • Coffee Consumption
  • Delayed Sleep
  • Earwax Type
  • Endurance vs Power
  • Exercise Impact on Weight
  • Eye Color
  • Freckling
  • Hair Curl and Texture
  • Hand Grip Strength
  • Height
  • Lactose Tolerance
  • Sleep Duration
  • Sleep Movement
  • Sleeplessness
  • Sweet Tooth
  • Tan vs. Sunburn
  • Waist Size

Those who test positive for a disease-causing FH variant will be referred by AdventHealth for medical laboratory blood testing, genetic counseling, and a cardiologist visit, reported the Ormond Beach Observer.

One in 250 people have FH, and 90% of them are undiagnosed, according to the FH Foundation, which also noted that children have a 50% chance of inheriting FH from parents with the condition.

AdventHealth plans to expand the free testing beyond central Florida to its 46 other hospitals located in nine states, Modern Healthcare noted.

Other Genetics Data Company/Healthcare Provider Partnerships

In Nevada, Helix partnered with the Renown Health Institute for Health Innovation (IHI) and the Desert Research Institute (DRI) to sequence 30,000 people for FH as part of the state’s Healthy Nevada Project (HNP).

Helix (above) is one of the world’s largest CLIA-certified, CAP-accredited next-generation sequencing labs. The partnership with AdventHealth offered study participants Exome+: a panel-grade medical exome enhanced by more than 300,000 informative non-coding regions; a co-branded ancestry + traits DNA product for all participants; secure storage of genomic data for the lifetime of the participant; infrastructure and data to facilitate research; and in-house clinical and scientific expertise, according to Helix’s website. (Photo copyright: Orlando Sentinel.)

Business Insider noted that Helix has focused on clinical partnerships for about a year and seems to be filling a niche in the genetic testing market.

“Helix is able to sidestep the costs of direct-to-consumer marketing and clinical test development, while still expanding its customer base through predefined hospital networks. And the company is in a prime position to capitalize on providers’ interest in population health management,” Business Insider reported.

Another genomics company, Color of Burlingame, Calif., also has population genomics programs with healthcare networks, including NorthShore University Health System in Ill.; Ochsner Health System in La.; and Jefferson Health in Philadelphia.

Ochsner’s program is the first “fully digital population health program” aimed at including clinical genomics data in primary care in an effort to affect patients’ health, FierceHealthcare reported.

In a statement, Ochsner noted that its innovationOchsner (iO) program screens selected patients for:

  • Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2 genes;
  • Lynch syndrome, associated with colorectal and other cancers; and
  • FH.

Color also offers genetic testing and whole genome sequencing services to NorthShore’s DNA10K program, which plans to test 10,000 patients for risk for hereditary cancers and heart diseases, according to news release.

And, Jefferson Health offered Color’s genetic testing to the healthcare system’s 33,000 employees, 10,000 of which signed up to learn their health risks as well as ancestry, a Color blog post states.

Conversely, Dark Daily recently reported on two Boston healthcare systems that started their own preventative gene sequencing clinics. The programs are operated by Brigham and Women’s Hospital and Massachusetts General Hospital (MGH).

And a Precision Medicine Institute e-briefing reported on Geisinger Health and Sanford Health’s move to offer genetic tests and precision medicine services in primary care clinics.

“Understanding the genome warning signals of every patient will be an essential part of wellness planning and health management,” said Geisinger Chief Executive Officer David Feinberg, MD, when he announced the new initiative at the HLTH (Health) Conference in Las Vegas. “Geisinger patients will be able to work with their family physician to modify their lifestyle and minimize risks that may be revealed,” he explained. “This forecasting will allow us to provide truly anticipatory healthcare instead of the responsive sick care that has long been the industry default across the nation.”

It will be interesting to see how and if genetic tests—free or otherwise—will advance precision medicine goals and population health treatments. It’s important for medical laboratory leaders to be involved in health network agreements with genetic testing companies. And clinical laboratories should be informed whenever private companies share their test results data with patients and primary care providers. 

—Donna Marie Pocius

Related Information:

It May Be Your DNA: First Large-Scale DNA Study in Florida Aims to Unlock the Secret to a Healthier Life

AdventHealth Offers Free DNA Tests to 10,000 Floridians

How AdventHealth Orlando is Building a Future in Genomics

Helix Partners with AdventHealth to Offer 10,000 Genetic Screenings in Florida

AdventHealth to Launch Large Genetic Study for High Cholesterol

Ochsner Health System Teaming Up with Genetic Testing Company Color in Population Genomics

The Healthy Nevada Project: from Recruitment to Real-World Impact

Ochsner Health System to Pilot Genetic Screening Program in Partnership with Color

North Shore and Color Unlock the Power of Genomics in Routine Care

Jefferson Heath and Color Advancing Precision Health Through Clinical Genomics and Richer Data

Two Boston Health Systems Enter the Growing Direct-to-Consumer Gene Sequencing Market by Opening Preventative Genomics Clinics, But Can Patients Afford the Service

Geisinger Health and Sanford Health Ready to Offer Genetic Tests and Precision Medicine Services in Primary Care Clinics

Proteomics May Hold Key to Understanding Aging’s Role in Chronic Diseases and Be Useful as a Clinical Laboratory Test for Age-related Diseases

Researchers are discovering it’s possible to determine a person’s age based on the amount of protein in the blood, but the technology isn’t always correct

Mass spectrometry is increasingly finding its way into clinical laboratories and with it—proteomics—the study of proteins in the human body. And like the human genome, scientists are discovering that protein plays an integral part in the aging process.

This is a most interesting research finding. Might medical laboratories someday use proteomic biomarkers to help physicians gauge the aging progression in patients? Might this diagnostic capability give pathologists and laboratory leaders a new product line for direct-to-consumer testing that would be a cash-paying, fast-growing, profitable clinical laboratory testing service? If so, proteomics could be a boon to clinical laboratories worldwide.

When research into genomics was brand-new, virtually no one imagined that someday the direct-to-consumer lab testing model would offer genetic testing to the public and create a huge stream of revenue for clinical laboratories that process genetic tests. Now, research into protein and aging might point to a similar possibility for proteomics.

For example, through proteomics, researchers led by Benoit Lehallier, PhD, Biostatistician, Instructor of Neurology and Neurological Sciences, and senior author Tony Wyss-Coray, PhD, Professor of Neurology and Neurological Sciences and co-director of the Stanford Alzheimer’s Disease Research Center at Stanford University in California, gained an understanding of aging that suggest intriguing possibilities for clinical laboratories.

In their study, published in Nature, titled, “Undulating Changes in Human Plasma Proteome Profiles Across the Lifespan,” the scientists stated that aging doesn’t happen in a consistent process over time, reported Science Alert.  

The Stanford researchers also found that they can accurately determine a person’s age based on the levels of certain proteins in his or her blood.

Additionally, the study of proteomics may finally explain why blood from young people can have a rejuvenating effect on elderly people’s brains, noted Scientific American.

Each of these findings is important on its own, but taken together, they may have interesting implications for pathologists who follow the research. And medical laboratory leaders may find opportunities in mass spectrometry in the near future, rather than decades from now.

Three Distinct Stages in Aging and Other Findings

The Stanford study found that aging appears to happen at three distinct points in a person’s life—around the ages 34, 60, and 78—rather than being a slow, steady process.

The researchers measured and compared levels of nearly 3,000 specific proteins in blood plasma taken from healthy people between the ages of 18 and 95 years. In the published study, the authors wrote, “This new approach to the study of aging led to the identification of unexpected signatures and pathways that might offer potential targets for age-related diseases.”

Along with the findings regarding the timeline for aging, the researchers found that about two-thirds of the proteins that change with age differ significantly between men and women. “This supports the idea that men and women age differently and highlights the need to include both sexes in clinical studies for a wide range of diseases,” noted a National Institutes of Health (NIH) report.

“We’ve known for a long time that measuring certain proteins in the blood can give you information about a person’s health status—lipoproteins for cardiovascular health, for example,” stated Wyss-Coray in the NIH report. “But it hasn’t been appreciated that so many different proteins’ levels—roughly a third of all the ones we looked at—change markedly with advancing age.”

Tony Wyss-Coray, PhD (above), Professor of Neurology and Neurological Sciences at Stanford University, was senior author of the proteomics study that analyzed blood plasma from 4,263 people between the ages 18-95. “Proteins are the workhorses of the body’s constituent cells, and when their relative levels undergo substantial changes, it means you’ve changed, too,” he said in a Stanford Medicine news article. “Looking at thousands of them in plasma gives you a snapshot of what’s going on throughout the body.” (Photo copyright: Stanford University.)

Differentiating Aging from Disease

Previous research studies also found it is indeed possible to measure a person’s age from his or her “proteomic signature.”

Toshiko Tanaka, PhD, Research Associate with the Longitudinal Study Section, Translational Gerontology Branch, National Institute of Aging (NIG), National Institute of Health (NIH), Baltimore, led a study into proteomics which concluded that more than 200 proteins are associated with age.

The researchers published their findings in Aging Cell, a peer-reviewed open-access journal of the Anatomical Society in the UK, titled, “Plasma Proteomic Signature of Age in Healthy Humans.” In it, the authors wrote, “Our results suggest that there are stereotypical biological changes that occur with aging that are reflected by circulating proteins.”

The fact that chronological age can be determined through a person’s proteomic signature suggests researchers could separate aging from various diseases. “Older age is the main risk factor for a myriad of chronic diseases, and it is invariably associated with progressive loss of function in multiple physiological systems,” wrote the researchers, adding, “A challenge in the field is the need to differentiate between aging and diseases.”

Can Proteins Cause Aging?

Additionally, the Stanford study found that changes in protein levels might not simply be a characteristic of aging, but may actually cause it, a Stanford Medicine news article notes.

“Changes in the levels of numerous proteins that migrate from the body’s tissues into circulating blood not only characterize, but quite possibly cause, the phenomenon of aging,” Wyss-Coray said.

Can Proteins Accurately Predict Age? Not Always

There were, however, some instances where the protein levels inaccurately predicted a person’s age. Some of the samples the Stanford researchers used were from the LonGenity research study conducted by the Albert Einstein College of Medicine, which investigated “why some people enjoy extremely long life spans, with physical health and brain function far better than expected in the 9th and 10th decades of life,” the study’s website notes.

That study included a group of exceptionally long-lived Ashkenazi Jews, who have a “genetic proclivity toward exceptionally good health in what for most of us is advanced old age,” according to the Stanford Medicine news article.

“We had data on hand-grip strength and cognitive function for that group of people. Those with stronger hand grips and better measured cognition were estimated by our plasma-protein clock to be younger than they actually were,” said Wyss-Coray. So, physical condition is a factor in proteomics’ ability to accurately prediction age.

Although understanding the connections between protein in the blood, aging, and disease is in early stages, it is clear additional research is warranted. Not too long ago the idea of consumers having their DNA sequenced from a home kit for fun seemed like fantasy.

However, after multiple FDA approvals, and the success of companies like Ancestry, 23andMe, and the clinical laboratories that serve them, the possibility that proteomics might go the same route does not seem so far-fetched.

—Dava Stewart

Related Information:

Our Bodies Age in Three Distinct Shifts, According to More than 4,000 Blood Tests

Fountain of Youth? Young Blood Infusions ‘Rejuvenate’ Old Mice

Undulating Changes in Human Plasma Proteome Profiles Across the Lifespan

Blood Protein Signatures Change Across Lifespan

Plasma Proteomic Signature of Age in Healthy Humans

Stanford Scientists Reliably Predict People’s Age by Measuring Proteins in Blood

Advancements That Could Bring Proteomics and Mass Spectrometry to Clinical Laboratories

Might Proteomics Challenge the Cult of DNA-centricity? Some Clinical Laboratory Diagnostic Developers See Opportunity in Protein-Centered Diagnostics

Advancements That Could Bring Proteomics and Mass Spectrometry to Clinical Laboratories

Experts list the top challenges facing widespread adoption of proteomics in the medical laboratory industry

Year-by-year, clinical laboratories find new ways to use mass spectrometry to analyze clinical specimens, producing results that may be more precise than test results produced by other methodologies. This is particularly true in the field of proteomics.

However, though mass spectrometry is highly accurate and fast, taking only minutes to convert a specimen into a result, it is not fully automated and requires skilled technologists to operate the instruments.

Thus, although the science of proteomics is advancing quickly, the average pathology laboratory isn’t likely to be using mass spectrometry tools any time soon. Nevertheless, medical laboratory scientists are keenly interested in adapting mass spectrometry to medical lab test technology for a growing number of assays.

Molly Campbell, Science Writer and Editor in Genomics, Proteomics, Metabolomics, and Biopharma at Technology Networks, asked proteomics experts “what, in their opinion, are the greatest challenges currently existing in proteomics, and how can we look to overcome them?” Here’s a synopsis of their answers:

Lack of High Throughput Impacts Commercialization

Proteomics isn’t as efficient as it needs to be to be adopted at the commercial level. It’s not as efficient as its cousin genomics. For it to become sufficiently efficient, manufacturers must be involved.

John Yates III, PhD, Professor, Department of Molecular Medicine at Scripps Research California campus, told Technology Networks, “One of the complaints from funding agencies is that you can sequence literally thousands of genomes very quickly, but you can’t do the same in proteomics. There’s a push to try to increase the throughput of proteomics so that we are more compatible with genomics.”

For that to happen, Yates says manufacturers need to continue advancing the technology. Much of the research is happening at universities and in the academic realm. But with commercialization comes standardization and quality control.

“It’s always exciting when you go to ASMS [the conference for the American Society for Mass Spectrometry] to see what instruments or technologies are going to be introduced by manufacturers,” Yates said.

There are signs that commercialization isn’t far off. SomaLogic, a privately-owned American protein biomarker discovery and clinical diagnostics company located in Boulder, Colo., has reached the commercialization stage for a proteomics assay platform called SomaScan. “We’ll be able to supplant, in some cases, expensive diagnostic modalities simply from a blood test,” Roy Smythe, MD, CEO of SomaLogic, told Techonomy.


The graphic above illustrates the progression mass spectrometry took during its development, starting with small proteins (left) to supramolecular complexes of intact virus particles (center) and bacteriophages (right). Because of these developments, today’s medical laboratories have more assays that utilize mass spectrometry. (Photo copyright: Technology Networks/Heck laboratory, Utrecht University, the Netherlands.)

Achieving the Necessary Technical Skillset

One of the main reasons mass spectrometry is not more widely used is that it requires technical skill that not many professionals possess. “For a long time, MS-based proteomic analyses were technically demanding at various levels, including sample processing, separation science, MS and the analysis of the spectra with respect to sequence, abundance and modification-states of peptides and proteins and false discovery rate (FDR) considerations,” Ruedi Aebersold, PhD, Professor of Systems Biology at the Institute of Molecular Systems Biology (IMSB) at ETH Zurich, told Technology Networks.

Aebersold goes on to say that he thinks this specific challenge is nearing resolution. He says that, by removing the problem created by the need for technical skill, those who study proteomics will be able to “more strongly focus on creating interesting new biological or clinical research questions and experimental design.”

Yates agrees. In a paper titled, “Recent Technical Advances in Proteomics,” published in F1000 Research, a peer-reviewed open research publishing platform for scientists, scholars, and clinicians, he wrote, “Mass spectrometry is one of the key technologies of proteomics, and over the last decade important technical advances in mass spectrometry have driven an increased capability of proteomic discovery. In addition, new methods to capture important biological information have been developed to take advantage of improving proteomic tools.”

No High-Profile Projects to Stimulate Interest

Genomics had the Human Genome Project (HGP), which sparked public interest and attracted significant funding. One of the big challenges facing proteomics is that there are no similarly big, imagination-stimulating projects. The work is important and will result in advances that will be well-received, however, the field itself is complex and difficult to explain.

Emanuel Petricoin, PhD, is a professor and co-director of the Center for Applied Proteomics and Molecular Medicine at George Mason University. He told Technology Networks, “the field itself hasn’t yet identified or grabbed onto a specific ‘moon-shot’ project. For example, there will be no equivalent to the human genome project, the proteomics field just doesn’t have that.”

He added, “The equipment needs to be in the background and what you are doing with it needs to be in the foreground, as is what happened in the genomics space. If it’s just about the machinery, then proteomics will always be a ‘poor step-child’ to genomics.”

Democratizing Proteomics

Alexander Makarov, PhD, is Director of Research in Life Sciences Mass Spectrometry (MS) at Thermo Fisher Scientific. He told Technology Networks that as mass spectrometry grew into the industry we have today, “each new development required larger and larger research and development teams to match the increasing complexity of instruments and the skyrocketing importance of software at all levels, from firmware to application. All this extends the cycle time of each innovation and also forces [researchers] to concentrate on solutions that address the most pressing needs of the scientific community.”

Makarov describes this change as “the increasing democratization of MS,” and says that it “brings with it new requirements for instruments, such as far greater robustness and ease-of-use, which need to be balanced against some aspects of performance.”

One example of the increasing democratization of MS may be several public proteomic datasets available to scientists. In European Pharmaceutical Review, Juan Antonio Viscaíno, PhD, Proteomics Team Leader at the European Bioinformatics Institute (EMBL-EBI) wrote, “These datasets are increasingly reused for multiple applications, which contribute to improving our understanding of cell biology through proteomics data.”

Sparse Data and Difficulty Measuring It

Evangelia Petsalaki, PhD, Group Leader EMBL-EBI, told Technology Networks there are two related challenges in handling proteomic data. First, the data is “very sparse” and second “[researchers] have trouble measuring low abundance proteins.”

Petsalaki notes, “every time we take a measurement, we sample different parts of the proteome or phosphoproteome and we are usually missing low abundance players that are often the most important ones, such as transcription factors.” She added that in her group they take steps to mitigate those problems.

“However, with the advances in MS technologies developed by many companies and groups around the world … and other emerging technologies that promise to allow ‘sequencing’ proteomes, analogous to genomes … I expect that these will not be issues for very long.”

So, what does all this mean for clinical laboratories? At the current pace of development, its likely assays based on proteomics could become more common in the near future. And, if throughput and commercialization ever match that of genomics, mass spectrometry and other proteomics tools could become a standard technology for pathology laboratories.

—Dava Stewart

Related Information:

5 Key Challenges in Proteomics, As Told by the Experts

The Evolution of Proteomics—Professor John Yates

The Evolution of Proteomics—Professor Ruedi Aebersold

The Evolution of Proteomics—Professor Emanuel Petricoin

The Evolution of Proteomics—Professor Alexander Makarov

The Evolution of Proteomics—Dr. Evangelia Petsalaki

For a Clear Read on Our Health, Look to Proteomics

Recent Technical Advances in Proteomics

Emerging Applications in Clinical Mass Spectrometry

HPP Human Proteome Project

Open Data Policies in Proteomics Are Starting to Revolutionize the Field

Native Mass Spectrometry: A Glimpse Into the Machinations of Biology

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