Proteins in human saliva make up its proteome and may be the key to new, precision medicine diagnostics that would give clinical pathologists new capabilities to identify disease
Clinical pathologists may soon have an array of new precision medicine diagnostic tools based on peoples’ saliva. There are an increasing number of “–omes” that can be the source of useful diagnostic biomarkers for developing clinical laboratory tests. The latest is the world’s first saliva protein biome wiki.
Called the Human Salivary Proteome Wiki (HSP Wiki), the “public data platform,” which was created by researchers at the University of Buffalo, is the “first of its kind,” according to Labroots, and “contains data on the many thousands of proteins present in saliva.”
The HSP Wiki brings together data from independent studies on proteins present in human saliva. One of the researchers’ goals is to speed up the development of saliva-based diagnostics and personalized medicine tools.
In “The Human Salivary Proteome Wiki: A Community-Driven Research Platform,” published in the Journal of Dental Research, the researchers wrote, “Saliva has become an attractive body fluid for on-site, remote, and real-time monitoring of oral and systemic health. At the same time, the scientific community needs a saliva-centered information platform that keeps pace with the rapid accumulation of new data and knowledge by annotating, refining, and updating the salivary proteome catalog.
“We developed the Human Salivary Proteome (HSP) Wiki as a public data platform for researching and retrieving custom-curated data and knowledge on the saliva proteome. … The HSP Wiki will pave the way for harnessing the full potential of the salivary proteome for diagnosis, risk prediction, therapy of oral and systemic diseases, and preparedness for emerging infectious diseases,” they concluded.
“This community-based data and knowledge base will pave the way to harness the full potential of the salivary proteome for diagnosis, risk prediction, and therapy for oral and systemic diseases, and increase preparedness for future emerging diseases and pandemics,” Stefan Ruhl, DDS, PhD (above right, with Omer Gokcumen, PhD, Associate Professor of Biological Sciences on left), Professor, Department of Oral Biology, University of Buffalo, and lead researcher of the study, told Labroots. Development of precision medicine clinical laboratory diagnostics is part of their research goals. (Photo copyright: University of Buffalo.)
Where Does Saliva Come From?
Saliva is a complex biological fluid that has long been linked to oral health and the health of the upper gastrointestinal tract. Only recently, though, have scientists begun to understand from where in the body saliva proteins originate.
The authors wrote: “Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract, and they serve as potential diagnostic markers for monitoring human health and disease. However, their precise organ origins remain unclear.
“Through transcriptomic analysis of major adult and fetal salivary glands and integration with the saliva proteome, the blood plasma proteome, and transcriptomes of 28+ organs, we link human saliva proteins to their source, identify salivary-gland-specific genes, and uncover fetal- and adult-specific gene repertoires,” they added.
“Our results pave the way for future investigations into glandular biology and pathology, as well as saliva’s use as a diagnostic fluid,” the researchers concluded.
Saliva plays a crucial role in digestion by breaking down starches. It also provides a protective barrier in the mouth. When salivary glands malfunction, patients can face serious health consequences. Although clinicians and scientists have long understood the importance of saliva to good health, the question now is whether it contains markers of specific diseases.
“The Human Salivary Proteome Wiki contains proteomic, genomic, transcriptomic data, as well as data on the glycome, sugar molecules present on salivary glycoproteins. New data goes through an interdisciplinary team of curators, which ensures that all input data is accurate and scientifically sound,” noted Labroots.
The graphic above “shows the interconnectedness of the thousands of salivary proteins originating from blood plasma, parotid glands, and submandibular and sublingual glands. The diagram is one of many tools available to researchers and clinicians through the Human Salivary Proteome Wiki,” noted a UBNow blog post. (Graphic copyright: University of Buffalo.)
Omics and Their Role in Clinical Laboratory Diagnostics
Proteomics is just one of several hotly-researched -omics that hold the potential to develop into important personalized medicine and diagnostics tools for pathologists. Genomics is a related area of research being studied for its potential to benefit precision medicine diagnostics.
However, unlike genomes, which do not change, proteomes change constantly. That is one of the main reasons studying the human salivary proteome could lead to valuable diagnostics tools.
Combining the study of the -omes with tools like mass spectrometry, a new era of pathology may be evolving. “With the rapid decrease in the costs of omics technologies over the past few years, whole-proteome profiling from tissue slides has become more accessible to diagnostic labs as a means of characterization of global protein expression patterns to evaluate the pathophysiology of diseases,” noted Pathology News.
Saliva and the Age of Precision Medicine
The study of the -omes may be an important element in the evolution of precision medicine, because of its ability to provide information about what is happening in patients’ bodies at the point of care.
Thus, a full understanding of the proteome of saliva and what causes it to change in response to different health conditions and diseases could open the door to an entirely new branch of diagnostics and laboratory medicine. It is easy and non-invasive to gather and, given that saliva contains so much information, it offers an avenue of study that may improve patients’ lives.
It also would bring us closer to the age of precision medicine where clinical laboratory scientists and pathologists can contribute even more value to referring physicians and their patients.
The study ‘shows that measurement using a urine test provides improved accuracy relative to other measurement methods, for example certain kinds of blood tests,’ a KI news release states
Researchers at the Karolinska Institute (KI) in Sweden have developed a non-invasive urine-based test that can identify what type of asthma a patient has and its severity. If developed into a clinical laboratory diagnostic, such a test also could give clinicians a better idea of what treatment is more likely to be effective—a core goal of precision medicine.
Another benefit of this methodology is that it is a non-invasive test. Should further studies conclude that this urine-based test produces accurate results acceptable for clinical settings, medical laboratories would certainly be interested in offering this assay, particularly for use in pediatric patients who are uncomfortable with the venipunctures needed to collect blood specimens. Also, given the incidence of asthma in the United States, there is the potential for a urine-based asthma test to generate a substantial number of test requests.
The objective of the study, according to the Karolinska Institute researchers, was “To test if urinary eicosanoid metabolites can direct asthma phenotyping.” The team used mass spectrometry to measured certain lipid biomarkers (prostaglandins and leukotrienes), which are known to play a key role in the inflammation that occurs during asthma attacks.
According to a KI news release, “The study is based on data from the U-BIOPRED study (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes), which was designed to investigate severe asthma. The study included 400 participants with severe asthma, which often requires treatment with corticosteroid tablets, nearly 100 individuals with milder forms of asthma, and 100 healthy control participants.”
“We discovered particularly high levels of the metabolites of the mast cell mediator prostaglandin D2 and the eosinophil product leukotriene C4 in asthma patients with what is referred to as Type 2 inflammation. Using our methodology, we were able to measure these metabolites with high accuracy and link their levels to the severity and type of asthma,” said Johan Kolmert, PhD (above), a post-doctoral researcher at the Institute of Environmental Medicine, Karolina Institute, and first author of the study, in the KI news release. If perfected, such accuracy could lead to effective precision medicine clinical laboratory tests. (Photo copyright: Karolinska Institute.)
More Accurate Testing Could Lead to Biomarker-guided Precision Medicine
In the US alone, 25,131,132 people currently suffer from asthma, about five million of which are children under the age of 18, according to 2019 CDC statistics. The World Health Organization (WHO) reports that worldwide, “Asthma affected an estimated 262 million people in 2019 and caused 461,000 deaths.”
People with mild asthma may have good success using steroid inhalers. However, for those with moderate to severe asthma where inhalers are not effective, oral corticosteroids may also be necessary. But corticosteroids have been associated with high blood pressure and diabetes, among other negative side effects.
“To replace corticosteroid tablets, in recent times several biological medicines have been introduced to treat patients with Type 2 inflammation characterized by increased activation of mast cells and eosinophils,” said Sven-Erik Dahlén, Professor at the Institute of Environmental Medicine, Karolinska Institute, in the news release.
Currently, there are no simple tests that show what type of asthma a patient has. Instead, clinicians rely on lung function tests, patient interviews, allergy tests, and blood tests.
Earlier this year, researchers at Brigham and Women’s Hospital and Exosome Diagnostics in Massachusetts investigated a non-invasive, urine-based test for transplant rejection. According to a news release, “Patients can spend up to six years waiting for a kidney transplant. Even when they do receive a transplant, up to 20% of patients will experience rejection.”
“If rejection is not treated, it can lead to scarring and complete kidney failure. Because of these problems, recipients can face life-long challenges,” said Jamil Azzi, MD, Director of the Kidney Transplantation Fellowship Program at Brigham and Women’s Hospital, and Associate Professor of Medicine at Harvard School of Medicine. “Our goal is to develop better tools to monitor patients without performing unnecessary biopsies. We try to detect rejection early, so we can treat it before scarring develops,” he said.
Detecting Bladder Cancer with Urine Testing
Another condition where urine tests are being investigated is bladder cancer. An article in Trends in Urology and Men’s Health states, “Several point-of-care urine tests have been developed to help identify patients who may be at higher risk of bladder cancer.” Those tests could have the potential for use in primary care, which could mean fewer people would need invasive, painful, and risk-carrying cystoscopies.
“New tests to help identify hematuria patients who are at a higher risk of cancer would help to improve the diagnostic pathway, reduce the number diagnosed by emergency presentation, lessen the burden on urology services, and spare those who do not have cancer an invasive and costly examination, such as cystoscopy,” the article’s authors wrote.
These urine-based tests are still under investigation by various research teams and more research is needed before clinical trials can be conducted and the tests can be submitted for regulatory approval. Though still in the early stages of development, urine-based diagnostic testing represents far less invasive, and therefore safer, ways to identify and treat various diseases.
Studies into how the elements in urine might be used as biomarkers for clinical laboratory tests may lead to improved non-invasive precision medicine diagnostics that could save many lives.
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.”
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.
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.
Should greater attention be given to protein damage in chronic diseases such as Alzheimer’s and diabetes? One life scientist says “yes” and suggests changing how test developers view the cause of age-related and degenerative diseases
DNA and the human genome get plenty of media attention and are considered by many to be unlocking the secrets to health and long life. However, as clinical laboratory professionals know, DNA is just one component of the very complex organism that is a human being.
In fact, DNA, RNA, and proteins are all valid biomarkers for medical laboratory tests and, according to one life scientist, all three should get equal attention as to their role in curing disease and keeping people healthy.
Along with proteins and RNA, DNA is actually an “equal partner in the circle of life,” wrote David Grainger, PhD, CEO of Methuselah Health, in a Forbes opinion piece about what he calls the “cult of DNA-centricity” and its relative limitations.
Effects of Protein Damage
“Aging and age-related degenerative diseases are caused by protein damage rather than by DNA damage,” explained Grainger, a Life Scientist who studies the role proteins play in aging and disease. “DNA, like data, cannot by itself do anything. The data on your computer is powerless without apps to interpret it, screens and speakers to communicate it, keyboards and touchscreens to interact with it.”
“Similarly,” he continued, “the DNA sequence information (although it resides in a physical object—the DNA molecule—just as computer data resides on a hard disk) is powerless and ethereal until it is translated into proteins that can perform functions,” he points out.
According to Grainger, diseases such as cystic fibrosis and Duchenne Muscular Dystrophy may be associated with genetic mutation. However, other diseases take a different course and are more likely to develop due to protein damage, which he contends may strengthen in time, causing changes in cells or tissues and, eventually, age-related diseases.
“Alzheimer’s disease, diabetes, or autoimmunity often take decades to develop (even though your genome sequence has been the same since the day you were conceived); the insidious accumulation of the damaged protein may be very slow indeed,” he penned.
“But so strong is the cult of DNA-centricity that most scientists seem unwilling to challenge the fundamental assumption that the cause of late-onset diseases must lie somewhere in the genome,” Grainger concludes.
Shifting Focus from Genetics to Proteins
Besides being CEO of Methuselah Health, Grainger also is Co-Founder and Chief Scientific Advisor at Medicxi, a life sciences investment firm that backed Methuselah Health with $5 million in venture capital funding for research into disease treatments that focus on proteins in aging, reported Fierce CEO.
Methuselah Health, founded in 2015 in Cambridge, UK, with offices in the US, is reportedly using post-translational modifications for analysis of many different proteins.
“At Methuselah Health, we have shifted focus from the genetics—which tells you in an ideal world how your body would function—to the now: this is how your body functions now and this is what is going wrong with it. And that answer lies in the proteins,” stated Dr. David Grainger (above), CEO of Methuselah Health, in an interview with the UK’s New NHS Alliance. Click on this link to watch the full interview. [Photo and caption copyright: New NHS Alliance.]
How Does it Work?
This is how Methuselah Health analyzes damaged proteins using mass spectrometry, according to David Mosedale, PhD, Methuselah Health’s Chief Technology Officer, in the New NHS Alliance story:
Protein samples from healthy individuals and people with diseases are used;
Proteins from the samples are sliced into protein blocks and fed slowly into a mass spectrometer, which accurately weighs them;
Scientists observe damage to individual blocks of proteins;
Taking those blocks, proteins are reconstructed to ascertain which proteins have been damaged;
Information is leveraged for discovery of drugs to target diseases.
Mass spectrometry is a powerful approach to protein sample identification, according to News-Medical.Net. It enables analysis of protein specificity and background contaminants. Interactions among proteins—with RNA or DNA—also are possible with mass spectrometry.
Methuselah Health’s scientists are particularly interested in the damaged proteins that have been around a while, which they call hyper-stable danger variants (HSDVs) and consider to be the foundation for development of age-related diseases, Grainger told WuXi AppTec.
“By applying the Methuselah platform, we can see the HSDVs and so understand which pathways we need to target to prevent disease,” he explained.
For clinical laboratories, pathologists, and their patients, work by Methuselah Health could accelerate the development of personalized medicine treatments for debilitating chronic diseases. Furthermore, it may compel more people to think of DNA as one of several components interacting that make up human bodies and not as the only game in diagnostics.
