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Clinical Laboratories and Pathology Groups

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Human Salivary Proteome Wiki Developed at University of Buffalo May Provide Biomarkers for New Diagnostic Tools and Medical Laboratory Tests

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.

Stefan Ruhl, DDS, PhD and Omer Gokcumen, PhD

“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 researchers of a study published in Cell Reports, titled, “Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva” sought to better understand the sources of saliva.

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.

Graphic of whole saliva

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.

In “Precision Medicine: Establishing Proteomic Assessment Criteria from Discovery to Clinical Diagnostics,” study authors Jennifer E. Van Eyk, PhD, Director, Advanced Clinical Biosystems Research Institute in the Department of Biomedical Sciences, and Kimia Sobhani, PhD, Director, ER and Cancer Center Laboratories and Associate Professor, Pathology and Laboratory Medicine, at Cedars-Sinai Medical Center, wrote, “The central goal of precision medicine is to provide the right treatment to the right patient at the right time based on their unique diagnosis/pathophysiological signature. Success relies on development of high-quality biomarkers to assist in diagnosis, prognosis, and risk stratification each patient.”

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.

Dava Stewart

Related Information:

The Human Salivary Proteome Wiki: A Community-Driven Research Platform

Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva

Researchers Create the First Saliva Wiki

Precision Medicine: Establishing Proteomic Assessment Criteria from Discovery to Clinical Diagnostics

Genomics and Proteomics and Interactomics, Oh, My! Researchers Conclude Metabolite-Protein Interactions are Important to Cellular Processes; Could New Omics Be Added to Clinical Laboratories’ Test Menus?

This potential new source of diagnostic biomarkers could give clinical labs a new tool to diagnose disease earlier and with greater accuracy

Clinical laboratories may soon have a new “omics” in their toolkit and vocabulary. In addition to genomics and proteomics, anatomic pathologists could also be using “interactomics” to diagnose disease earlier and with increased accuracy.

At least that’s what researchers at ETH Zurich (ETH), an international university for technology and natural sciences, have concluded. They published the results of their study in Cell.

“Here, we present a chemoproteomic workflow for the systematic identification of metabolite-protein interactions directly in their native environments,” the researchers wrote. “Our data reveal functional and structural principles of chemical communication, shed light on the prevalence and mechanisms of enzyme promiscuity, and enable extraction of quantitative parameters of metabolite binding on a proteome-wide scale.”

Interactomics address interactions between proteins and small molecules, according to an article published in Technology Networks. The terms “interactomics” and “omics” were inspired by research that described, for the first time, the interactions and relationships of all proteins and metabolites (A.K.A, small molecules) in the whole proteome.

Medical laboratories and anatomic pathologists have long understood the interactions among proteins, or between proteins and DNA or RNA. However, metabolite interactions with packages of proteins are not as well known.

These new omics could eventually be an important source of diagnostic biomarkers. They may, one day, contribute to lower cost clinical laboratory testing for some diseases, as well.

Metabolite-Protein Interactions are Key to Cellular Processes

The ETH researchers were motivated to explore the interplay between small molecules and proteins because they have important responsibilities in the body. These cellular processes include:

“Metabolite-protein interactions control a variety of cellular processes, thereby playing a major role in maintaining cellular homeostasis. Metabolites comprise the largest fraction of molecules in cells. But our knowledge of the metabolite-protein interaction lags behind our understanding of protein-protein or protein-DNA interactomes,” the researchers wrote in Cell.

Leveraging Limited Proteolysis and Mass Spectrometry

The researchers used limited proteolysis (LiP) technology with mass spectrometry to discover metabolite-protein interactions. Results aside, experts pointed out that the LiP technology itself is significant.

“It is one of the few methods that enables the unbiased and proteome-wide profiling of protein conformational changes resulting from interaction of proteins with compounds,” stated a Biognosys blog post.

Biognosys, a proteomics company founded in 2008, was originally part of a lab at ETH Zurich.

The ETH team focused on the E. coli bacterial cell in particular and how its proteins and enzymes interact with metabolites.

Paola Picotti PhD

“Although the metabolism of E. coli and associated molecules is already very well known, we succeeded in discovering many new interactions and the corresponding binding sites,” Paola Picotti, PhD, Professor of Molecular Systems Biology at ETH Zurich, who led the research, told Technology Networks. “The data that we produce with this technique will help to identify new regulatory mechanisms, unknown enzymes and new metabolic reactions in the cell,” she concluded. (Photo copyright: ETH Zurich.)

 

More than 1,000 New Interactions Discovered

The study progressed as follows, according to Technology Networks’ report:

  • “Cellular fluid, containing proteins, was extracted from bacterial cells;
  • “A metabolite was added to each sample;
  • “The metabolite interacted with proteins;
  • “Proteins were cut into smaller pieces by molecular scissors (A.K.A., CRISPR-Cas9);
  • “Protein structure was altered when it interacted with a metabolite;
  • “A different set of peptides emerged when the “molecular scissors” cut at different sites;
  • “Pieces of samples were measured with a mass spectrometer;
  • “Data were obtained, fed into a computer, and structural differences and changes were reconstructed;
  • “1,650 different protein-metabolite interactions were found;
  • “1,400 of those discovered were new.”

A Vast, Uncharted Metabolite-protein Interaction Network  

The research is a major step forward in the body of knowledge about interactions between metabolites and proteins and how they affect cellular processes, according to Balázs Papp, PhD, Principal Investigator, Biological Research Center of the Hungarian Academy of Sciences.

“Strikingly, more than 80% of the reported interactions were novel and about one quarter of the measured proteome interacted with at least one of the 20 tested metabolites. This indicates that the metabolite-protein interaction network is vast and largely uncharted,” Papp stated in an ETH Zurich Faculty of 1000 online article.

According to Technology Networks, “Picotti has already patented the method. The ETH spin-off Biognosys is the exclusive license holder and is now using the method to test various drugs on behalf of pharmaceutical companies.”

The pharmaceutical industry is reportedly interested in the approach as a way to ascertain drug interactions with cellular proteins and their effectiveness in patient care.

The ETH Zurich study is compelling, especially as personalized medicine takes hold and more medical laboratories and anatomic pathology groups add molecular diagnostics to their capabilities.

—Donna Marie Pocius 

Related Information:

The New “Omics”—Measuring Molecular Interactions

Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication

A New Study Maps Protein-Metabolite Interactions in an Unbiased Way

Cell Paper on Protein Metabolite Interactions Recommended in Faculty 1000 Twice

Rapid Progress in Systems Biology Predicted to Increase Multiplex Testing by Clinical Pathology Laboratories

Trend from reductionism to holistic biomedicine means clinical laboratories and pathologists should expect increased multiplex testing

Systems biology (SB) is a rapidly-evolving area of research that, by itself, could greatly expand the need for multiplex testing performed by clinical laboratories. But systems biology has yet to catch the full attention of either the media or Wall Street.

That may soon change. Despite the complexity of human metabolic systems, experts in systems biology are making progress in identifying the myriad of metabolic channels that collectively can be used to diagnose disease and identify appropriate therapies. These are auspicious developments for medical laboratory managers and pathologists.

Probably no single individual has done more to advance the field of systems biology than Leroy Hood, M.D., Ph.D. In 2000, he co-founded the Institute for Systems Biology (ISB) in Seattle, Washington and his colleagues engaged scientists across a number of fields to study the metabolic processes of humans and other organisms.
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