Metabolomics Community in Russia: History of Development, Key Participants, and Results

Metabolomics is the latest trend in the “-omics” sciences, of which technologies are widely used today in all life sciences. Metabolomics gave impetus to the description of biochemical processes that occur in many organisms, search for new biomarkers of disease, and laid the foundation for new clinical laboratory diagnostics. The purpose of this review is to show how metabolomics is represented in Russian science, what main research areas were chosen, and to demonstrate the successes and main achievements of Russian scientists in this field. The review is dedicated to the 10th anniversary of Russian metabolomics and also touches on the history of the formation of Russian metabolomics and prospects for the future

Current State and Future Perspectives on Personalized Metabolomics

Metabolomics is one of the most promising ‘omics’ sciences for the implementation in medicine by developing new diagnostic tests and optimizing drug therapy. Since in metabolomics, the end products of the biochemical processes in an organism are studied, which are under the influence of both genetic and environmental factors, the metabolomics analysis can detect any changes associated with both lifestyle and pathological processes. Almost every case-controlled metabolomics study shows a high diagnostic accuracy. Taking into account that metabolomics processes are already described for most nosologies, there are prerequisites that a high-speed and comprehensive metabolite analysis will replace, in near future, the narrow range of chemical analyses used today, by the medical community. However, despite the promising perspectives of personalized metabolomics, there are currently no FDA-approved metabolomics tests. The well-known problem of complexity of personalized metabolomics data analysis and their interpretation for the end-users, in addition to a traditional need for analytical methods to address the quality control, standardization, and data treatment are reported in the review. Possible ways to solve the problems and change the situation with the introduction of metabolomics tests into clinical practice, are also discussed

In Situ Mass Spectrometry Diagnostics of Impaired Glucose Tolerance Using Label-Free Metabolomic Signature

In metabolomics, mass spectrometry is used to detect a large number of low-molecular substances in a single analysis. Such a capacity could have direct application in disease diagnostics. However, it is challenging because of the analysis complexity, and the search for a way to simplify it while maintaining the diagnostic capability is an urgent task. It has been proposed to use the metabolomic signature without complex data processing (mass peak detection, alignment, normalization, and identification of substances, as well as any complex statistical analysis) to make the analysis more simple and rapid. Methods: A label-free approach was implemented in the metabolomic signature, which makes the measurement of the actual or conditional concentrations unnecessary, uses only mass peak relations, and minimizes mass spectra processing. The approach was tested on the diagnosis of impaired glucose tolerance (IGT). Results: The label-free metabolic signature demonstrated a diagnostic accuracy for IGT equal to 88% (specificity 85%, sensitivity 90%, and area under receiver operating characteristic curve (AUC) of 0.91), which is considered to be a good quality for diagnostics. Conclusions: It is possible to compile label-free signatures for diseases that allow for diagnosing the disease in situ, i.e., right at the mass spectrometer without complex data processing. This achievement makes all mass spectrometers potentially versatile diagnostic devices and accelerates the introduction of metabolomics into medicine

Evaluation of Dried Blood Spot Sampling for Clinical Metabolomics: Effects of Different Papers and Sample Storage Stability

The dried blood spot (DBS) sampling has a lot of advantages in comparison with the “standard” venous blood collecting, such as small collection volume, painless and easy sample collection with minimal training required, stable and transportable at ambient temperatures, etc. The aim of this study was to determine the comparability of four different types of DBS sampling (HemaSpot™-HF Blood Collection Device, Whatman® 903 Protein Saver Snap Apart Card, card ImmunoHealth™, and glass fiber strip ImmunoHealth™) for analysis of the global metabolites profile. All the samples were collected from the same person at the same time and stored at room temperature for four weeks in order to exclude all possible deviations deriving from biological variances and to evaluate sample storage stability. Metabolome profiling by direct injection of a deproteinized capillary blood DBS sample into an electrospray ion source of a hybrid quadrupole time-of-flight mass spectrometer was used. Differences in the metabolomics profile were found between the different DBS collection materials, especially for ImmunoHealth™ card and ImmunoHealth™ glass fiber strip. However, our results indicate that the analytical performance of all tested DBS sampling materials showed consistent results overall detected metabolites and no dramatic changes between them in the metabolic composition during the storage time

Holistic Metabolomic Laboratory-Developed Test (LDT): Development and Use for the Diagnosis of Early-Stage Parkinson’s Disease

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is developed and used within a single laboratory. The holistic metabolomic LDT integrating the currently available data on human metabolic pathways, changes in the concentrations of low-molecular-weight compounds in the human blood during diseases and other conditions, and their prevalent location in the body was developed. That is, the LDT uses all of the accumulated metabolic data relevant for disease diagnosis and high-resolution mass spectrometry with data processing by in-house software. In this study, the LDT was applied to diagnose early-stage Parkinson’s disease (PD), which currently lacks available laboratory tests. The use of the LDT for blood plasma samples confirmed its ability for such diagnostics with 73% accuracy. The diagnosis was based on relevant data, such as the detection of overrepresented metabolite sets associated with PD and other neurodegenerative diseases. Additionally, the ability of the LDT to detect normal composition of low-molecular-weight compounds in blood was demonstrated, thus providing a definition of healthy at the molecular level. This LDT approach as a screening tool can be used for the further widespread testing for other diseases, since ‘omics’ tests, to which the metabolomic LDT belongs, cover a variety of them

Potential Plasma Metabolite Biomarkers of Diabetic Nephropathy: Untargeted Metabolomics Study

Diabetic nephropathy (DN) is one of the specific complications of diabetes mellitus and one of the leading kidney-related disorders, often requiring renal replacement therapy. Currently, the tests commonly used for the diagnosis of DN, albuminuria (AU) and glomerular filtration rate (GFR), have limited sensitivity and specificity and can usually be noted when typical morphological changes in the kidney have already been manifested. That is why the extreme urgency of the problem of early diagnosis of this disease exists. The untargeted metabolomics analysis of blood plasma samples from 80 patients with type 1 diabetes and early and late stages of DN according to GFR was performed using direct injection mass spectrometry and bioinformatics analysis for diagnosing signatures construction. Among the dysregulated metabolites, combinations of 15 compounds, including amino acids and derivatives, monosaccharides, organic acids, and uremic toxins were selected for signatures for DN diagnosis. The selected metabolite combinations have shown high performance for diagnosing of DN, especially for the late stage (up to 99%). Despite the metabolite signature determined for the early stage of DN being characterized by a diagnostic performance of 81%, these metabolites as potential biomarkers might be useful in the evaluation of treatment of the disease, especially at early stages that may reduce the risk of kidney failure development

Metabolomic Laboratory-Developed Tests: Current Status and Perspectives

Laboratory-developed tests (LDTs) are a subset of in vitro diagnostic devices, which the US Food and Drug Administration defines as “tests that are manufactured by and used within a single laboratory”. The review describes the emergence and history of LDTs. The current state and development prospects of LDTs based on metabolomics are analyzed. By comparing LDTs with the scientific metabolomics study of human bio samples, the characteristic features of metabolomic LDT are shown, revealing its essence, strengths, and limitations. The possibilities for further developments and scaling of metabolomic LDTs and their potential significance for healthcare are discussed. The legal aspects of LDT regulation in the United States, European Union, and Singapore, demonstrating different approaches to this issue, are also provided. Based on the data presented in the review, recommendations were made on the feasibility and ways of further introducing metabolomic LDTs into practice

Personal Metabolomics: A Global Challenge

Today, the introduction of metabolomics, like other omics sciences, into clinical practice as a personal omics test that realizes the perfect analytical capabilities of this science has become an important subject. The assembled data show that the metabolome of biosamples is a collection of highly informative and accurate signatures of virtually all diseases that are widespread in the population. However, we have not seen the emergence of personalized metabolomics in clinical practice. This article analyzes the causes of this problem. The complexity of personal metabolic data analysis and its incompatibility with widely accepted data treatment in metabolomics are shown. As a result, the impossibility of translating metabolic signatures accumulated in databases into a personal test is revealed. Problem-solving strategies that may radically change the situation and realize the analytical capabilities of metabolomics in medical laboratory practice are discussed

Metabolome Profiling in Aging Studies

Organism aging is closely related to systemic metabolic changes. However, due to the multilevel and network nature of metabolic pathways, it is difficult to understand these connections. Today, scientists are trying to solve this problem using one of the main approaches of metabolomics—untargeted metabolome profiling. The purpose of this publication is to review metabolomic studies based on such profiling, both in animal models and in humans. This review describes metabolites that vary significantly across age groups and include carbohydrates, amino acids, carnitines, biogenic amines, and lipids. Metabolic pathways associated with the aging process are also shown, including those associated with amino acid, lipid, and energy metabolism. The presented data reveal the mechanisms of aging and can be used as a basis for monitoring biological age and predicting age-related diseases in the early stages of their development

Cell Proteomic Footprinting: Advances in the Quality of Cellular and Cell-Derived Cancer Vaccines

In omics sciences, many compounds are measured simultaneously in a sample in a single run. Such analytical performance opens up prospects for improving cellular cancer vaccines and other cell-based immunotherapeutics. This article provides an overview of proteomics technology, known as cell proteomic footprinting. The molecular phenotype of cells is highly variable, and their antigenic profile is affected by many factors, including cell isolation from the tissue, cell cultivation conditions, and storage procedures. This makes the therapeutic properties of cells, including those used in vaccines, unpredictable. Cell proteomic footprinting makes it possible to obtain controlled cell products. Namely, this technology facilitates the cell authentication and quality control of cells regarding their molecular phenotype, which is directly connected with the antigenic properties of cell products. Protocols for cell proteomic footprinting with their crucial moments, footprint processing, and recommendations for the implementation of this technology are described in this paper. The provided footprints in this paper and program source code for their processing contribute to the fast implementation of this technology in the development and manufacturing of cell-based immunotherapeutics