Current state-of-the-art of separation methods used in LC-MS based metabolomics and lipidomics.

Metabolomics deals with the large-scale analysis of metabolites, belonging to numerous compound classes and showing an extremely high chemical diversity and complexity. Lipidomics, being a subcategory of metabolomics, analyzes the cellular lipid species. Both require state-of-the-art analytical methods capable of accessing the underlying chemical complexity. One of the major techniques used for the analysis of metabolites and lipids is Liquid Chromatography-Mass Spectrometry (LC-MS), offering both different selectivities in LC separation and high sensitivity in MS detection. Chromatography can be divided into different modes, based on the properties of the employed separation system. The most popular ones are Reversed-Phase (RP) separation for non- to mid-polar molecules and Hydrophilic Interaction Liquid Chromatography (HILIC) for polar molecules. So far, no single analysis method exists that can cover the entire range of metabolites or lipids, due to the huge chemical diversity. Consequently, different separation methods have been used for different applications and research questions. In this review, we explore the current use of LC-MS in metabolomics and lipidomics. As a proxy, we examined the use of chromatographic methods in the public repositories EBI MetaboLights and NIH Metabolomics Workbench. We extracted 1484 method descriptions, collected separation metadata and generated an overview on the current use of columns, eluents, etc. Based on this overview, we reviewed current practices and identified potential future trends as well as required improvements that may allow us to increase metabolite coverage, throughput or both simultaneously.

Extending human healthspan and longevity: a symposium report.

For many years, it was believed that the aging process was inevitable and that age-related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age-related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life. Experts in the field have made remarkable advancements in understanding the mechanisms underlying biological aging and identified ways to target aging pathways using both novel agents and repurposed therapies. While geroscience researchers currently face significant barriers in bringing therapies through clinical development, proof-of-concept studies, as well as early-stage clinical trials, are underway to assess the feasibility of drug evaluation and lay a regulatory foundation for future FDA approvals in the future.

A Scoping Review of the Application of Metabolomics in Nutrition Research: The Literature Survey 2000-2019.

Nutrimetabolomics is an emerging field in nutrition research, and it is expected to play a significant role in deciphering the interaction between diet and health. Through the development of omics technology over the last two decades, the definition of food and nutrition has changed from sources of energy and major/micro-nutrients to an essential exposure factor that determines health risks. Furthermore, this new approach has enabled nutrition research to identify dietary biomarkers and to deepen the understanding of metabolic dynamics and the impacts on health risks. However, so far, candidate markers identified by metabolomics have not been clinically applied and more efforts should be made to validate those. To help nutrition researchers better understand the potential of its application, this scoping review outlined the historical transition, recent focuses, and future prospects of the new realm, based on trends in the number of human research articles from the early stage of 2000 to the present of 2019 by searching the Medical Literature Analysis and Retrieval System Online (MEDLINE). Among them, objective dietary assessment, metabolic profiling, and health risk prediction were positioned as three of the principal applications. The continued growth will enable nutrimetabolomics research to contribute to personalized nutrition in the future.

Recent Metabolic Advances for Preventing and Treating Acute and Chronic Graft Versus Host Disease.

The therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by the development of graft-versus-host disease (GVHD). In GVHD, rigorous pre-conditioning regimen resets the immune landscape and inflammatory milieu causing immune dysregulation, characterized by an expansion of alloreactive cells and a reduction in immune regulatory cells. In acute GVHD (aGVHD), the release of damage- and pathogen- associated molecular patterns from damaged tissue caused by the conditioning regimen sets the stage for T cell priming, activation and expansion further exacerbating tissue injury and organ damage, particularly in the gastrointestinal tract. Studies have shown that donor T cells utilize multiple energetic and biosynthetic pathways to mediate GVHD that can be distinct from the pathways used by regulatory T cells for their suppressive function. In chronic GVHD (cGVHD), donor T cells may differentiate into IL-21 producing T follicular helper cells or tissue resident T helper cells that cooperate with germinal center B cells or memory B cells, respectively, to produce allo- and auto-reactive antibodies with subsequent tissue fibrosis. Alternatively, donor T cells can become IFN- γ/IL-17 cytokine expressing T cells that mediate sclerodermatous skin injury. Patients refractory to the first line standard regimens for GVHD treatment have a poor prognosis indicating an urgent need for new therapies to restore the balance between effector and regulatory immune cells while preserving the beneficial graft-versus-tumor effect. Emerging data points toward a role for metabolism in regulating these allo- and auto-immune responses. Here, we will discuss the preclinical and clinical data available on the distinct metabolic demands of acute and chronic GVHD and recent efforts in identifying therapeutic targets using metabolomics. Another dimension of this review will examine the changing microbiome after allo-HSCT and the role of microbial metabolites such as short chain fatty acids and long chain fatty acids on regulating immune responses. Lastly, we will examine the metabolic implications of coinhibitory pathway blockade and cellular therapies in allo-HSCT. In conclusion, greater understanding of metabolic pathways involved in immune cell dysregulation during allo-HSCT may pave the way to provide novel therapies to prevent and treat GVHD.

Top Trends in Multiomics Research: Evaluation of 52 Published Studies and New Ways of Thinking Terminology and Visual Displays.

Multiomics study designs have significantly increased understanding of complex biological systems. The multiomics literature is rapidly expanding and so is their heterogeneity. However, the intricacy and fragmentation of omics data are impeding further research. To examine current trends in multiomics field, we reviewed 52 articles from PubMed and Web of Science, which used an integrated omics approach, published between March 2006 and January 2021. From studies, data regarding investigated loci, species, omics type, and phenotype were extracted, curated, and streamlined according to standardized terminology, and summarized in a previously developed graphical summary. Evaluated studies included 21 omics types or applications of omics technology such as genomics, transcriptomics, metabolomics, epigenomics, environmental omics, and pharmacogenomics, species of various phyla including human, mouse, Arabidopsis thaliana, Saccharomyces cerevisiae, and various phenotypes, including cancer and COVID-19. In the analyzed studies, diverse methods, protocols, results, and terminology were used and accordingly, assessment of the studies was challenging. Adoption of standardized multiomics data presentation in the future will further buttress standardization of terminology and reporting of results in systems science. This shall catalyze, we suggest, innovation in both science communication and laboratory medicine by making available scientific knowledge that is easier to grasp, share, and harness toward medical breakthroughs.

Ionomic Approaches for Discovery of Novel Stress-Resilient Genes in Plants.

Plants, being sessile, face an array of biotic and abiotic stresses in their lifespan that endanger their survival. Hence, optimized uptake of mineral nutrients creates potential new routes for enhancing plant health and stress resilience. Recently, minerals (both essential and non-essential) have been identified as key players in plant stress biology, owing to their multifaceted functions. However, a realistic understanding of the relationship between different ions and stresses is lacking. In this context, ionomics will provide new platforms for not only understanding the function of the plant ionome during stresses but also identifying the genes and regulatory pathways related to mineral accumulation, transportation, and involvement in different molecular mechanisms under normal or stress conditions. This article provides a general overview of ionomics and the integration of high-throughput ionomic approaches with other "omics" tools. Integrated omics analysis is highly suitable for identification of the genes for various traits that confer biotic and abiotic stress tolerance. Moreover, ionomics advances being used to identify loci using qualitative trait loci and genome-wide association analysis of element uptake and transport within plant tissues, as well as genetic variation within species, are discussed. Furthermore, recent developments in ionomics for the discovery of stress-tolerant genes in plants have also been addressed; these can be used to produce more robust crops with a high nutritional value for sustainable agriculture.

Advances in the Study of Metabolomics and Metabolites in Some Species Interactions.

In the natural environment, interactions between species are a common natural phenomena. The mechanisms of interaction between different species are mainly studied using genomic, transcriptomic, proteomic, and metabolomic techniques. Metabolomics is a crucial part of system biology and is based on precision instrument analysis. In the last decade, the emerging field of metabolomics has received extensive attention. Metabolomics not only provides a qualitative and quantitative method for studying the mechanisms of interactions between different species, but also helps clarify the mechanisms of defense between the host and pathogen, and to explore new metabolites with various biological activities. This review focuses on the methods and progress of interspecies metabolomics. Additionally, the prospects and challenges of interspecies metabolomics are discussed.

Unraveling mosquito metabolism with mass spectrometry-based metabolomics.

Nearly half a million people die annually due to mosquito-borne diseases. Despite aggressive mosquito population-control efforts, current strategies are limited in their ability to control these vectors. A better understanding of mosquito metabolism through modern approaches can contribute to the discovery of novel metabolic targets and/or regulators and lead to the development of better mosquito-control strategies. Currently, cutting-edge technologies such as gas or liquid chromatography-mass spectrometry-based metabolomics are considered 'mature technologies' in many life-science disciplines but are still an emerging area of research in medical entomology. This review primarily discusses recent developments and progress in the application of mass spectrometry-based metabolomics to answer multiple biological questions related to mosquito metabolism.

The evolving landscape of untargeted metabolomics.

AIMS: Untargeted Metabolomics is a "hypothesis-generating discovery strategy" that compares groups of samples (e.g., cases vs controls); identifies the metabolome and establishes (early signs of) perturbations. Targeted Metabolomics helped gather key information in life sciences and disclosed novel strategies for the treatment of major clinical entities (e.g., malignancy, cardiovascular diabetes mellitus, drug toxicity). Because of its relevance in biomarker discovery, attention is now devoted to improving the translational potential of untargeted Metabolomics. DATA SYNTHESIS: Expertise in laboratory medicine and in bioinformatics helps solve challenges/pitfalls that may bias metabolite profiling in untargeted Metabolomics. Clinical validation (availability/reliability of analytical instruments) and profitability (how many people will use the test) are mandatory steps for potential biomarkers. Biomarkers to predict individual patient response, patient populations that will best respond to specific strategies and/or approaches for an optimal response to treatment are now being developed. Additional help is expected from professional, and regulatory Agencies as to guidelines for study design and data acquisition and analysis, to be applied from the very beginning of a project. Evidence from food, plant, human, environmental, and animal research argues for the need of miniaturized approaches that employ low-cost, easy to use, mobile devices. ELISA kits with such characteristics that employ targeted metabolites are already available. CONCLUSIONS: Improving knowledge of the mechanisms behind the disease status (pathophysiology) will help untargeted Metabolomics gather a direct positive impact on welfare and industrial advancements, and fade uncertainties perceived by regulators/payers and patients concerning variables related to miniaturised instruments and user-friendly software and databases.

Multi-omics approaches to improve malaria therapy.

Malaria contributes to the most widespread infectious diseases worldwide. Even though current drugs are commercially available, the ever-increasing drug resistance problem by malaria parasites poses new challenges in malaria therapy. Hence, searching for efficient therapeutic strategies is of high priority in malaria control. In recent years, multi-omics technologies have been extensively applied to provide a more holistic view of functional principles and dynamics of biological mechanisms. We briefly review multi-omics technologies and focus on recent malaria progress conducted with the help of various omics methods. Then, we present up-to-date advances for multi-omics approaches in malaria. Next, we describe resistance phenomena to established antimalarial drugs and underlying mechanisms. Finally, we provide insight into novel multi-omics approaches, new drugs and vaccine developments and analyze current gaps in multi-omics research. Although multi-omics approaches have been successfully used in malaria studies, they are still limited. Many gaps need to be filled to bridge the gap between basic research and treatment of malaria patients. Multi-omics approaches will foster a better understanding of the molecular mechanisms of Plasmodium that are essential for the development of novel drugs and vaccines to fight this disastrous disease.

Spatially Resolved Mass Spectrometry at the Single Cell: Recent Innovations in Proteomics and Metabolomics.

Biological systems are composed of heterogeneous populations of cells that intercommunicate to form a functional living tissue. Biological function varies greatly across populations of cells, as each single cell has a unique transcriptome, proteome, and metabolome that translates to functional differences within single species and across kingdoms. Over the past decade, substantial advancements in our ability to characterize omic profiles on a single cell level have occurred, including in multiple spectroscopic and mass spectrometry (MS)-based techniques. Of these technologies, spatially resolved mass spectrometry approaches, including mass spectrometry imaging (MSI), have shown the most progress for single cell proteomics and metabolomics. For example, reporter-based methods using heavy metal tags have allowed for targeted MS investigation of the proteome at the subcellular level, and development of technologies such as laser ablation electrospray ionization mass spectrometry (LAESI-MS) now mean that dynamic metabolomics can be performed in situ. In this Perspective, we showcase advancements in single cell spatial metabolomics and proteomics over the past decade and highlight important aspects related to high-throughput screening, data analysis, and more which are vital to the success of achieving proteomic and metabolomic profiling at the single cell scale. Finally, using this broad literature summary, we provide a perspective on how the next decade may unfold in the area of single cell MS-based proteomics and metabolomics.

Nutrition and Rheumatoid Arthritis in the 'Omics' Era.

Modern high-throughput 'omics' science tools (including genomics, transcriptomics, proteomics, metabolomics and microbiomics) are currently being applied to nutritional sciences to unravel the fundamental processes of health effects ascribed to particular nutrients in humans and to contribute to more precise nutritional advice. Diet and food components are key environmental factors that interact with the genome, transcriptome, proteome, metabolome and the microbiota, and this life-long interplay defines health and diseases state of the individual. Rheumatoid arthritis (RA) is a chronic autoimmune disease featured by a systemic immune-inflammatory response, in genetically susceptible individuals exposed to environmental triggers, including diet. In recent years increasing evidences suggested that nutritional factors and gut microbiome have a central role in RA risk and progression. The aim of this review is to summarize the main and most recent applications of 'omics' technologies in human nutrition and in RA research, examining the possible influences of some nutrients and nutritional patterns on RA pathogenesis, following a nutrigenomics approach. The opportunities and challenges of novel 'omics technologies' in the exploration of new avenues in RA and nutritional research to prevent and manage RA will be also discussed.

Metabolomics: small molecules that matter more.

Metabolomics, an analytical study with high-throughput profiling, helps to understand interactions within a biological system. Small molecules, called metabolites or metabolomes with the size of <1500 Da, depict the status of a biological system in a different manner. Currently, we are in need to globally analyze the metabolome and the pathways involved in healthy, as well as diseased conditions, for possible therapeutic applications. Metabolome analysis has revealed high-abundance molecules during different conditions such as diet, environmental stress, microbiota, and disease and treatment states. As a result, it is hard to understand the complete and stable network of metabolites of a biological system. This review helps readers know the available techniques to study metabolomics in addition to other major omics such as genomics, transcriptomics, and proteomics. This review also discusses the metabolomics in various pathological conditions and the importance of metabolomics in therapeutic applications.

Metabolomic and Transcriptomic Profiling Provide Novel Insights into Fruit Ripening and Ripening Disorder Caused by 1-MCP Treatments in Papaya.

Treatment with 1-methylcyclopropylene (1-MCP) is an effective technique to preserve fruits, but inappropriate treatment with 1-MCP causes a ripening disorder (rubbery texture) in papaya fruit. In this study, a combined metabolomic and transcriptomic analysis was conducted to reveal the possible mechanism of the ripening disorder caused by unsuitable 1-MCP in papaya. A total of 203 differential accumulated metabolites (DAMs) were identified in the metabolome analysis. Only 24 DAMs were identified in the control (CK) vs. the 1-MCP 2 h group, and they were primarily flavonoids. Ninety and 89 DAMs were identified in the CK vs. 1-MCP 16 h and 1-MCP 2 h vs. 1-MCP 16 h groups, respectively, indicating that long-term 1-MCP treatment severely altered the metabolites during fruit ripening. 1-MCP 16 h treatment severely reduced the number of metabolites, which primarily consisted of flavonoids, lipids, phenolic acids, alkaloids, and organic acids. An integrated analysis of RNA-Seq and metabolomics showed that various energy metabolites for the tricarboxylic acid cycle were reduced by long-term treatment with 1-MCP, and the glycolic acid cycle was the most significantly affected, as well as the phenylpropane pathway. These results provide valuable information for fruit quality control and new insight into the ripening disorder caused by unsuitable treatment with 1-MCP in papaya.

[New technologies to unveil the role of brain glial cells]. / De nouvelles techniques pour dévoiler le rôle des cellules gliales du cerveau.

Brain function relies on complex interactions between neurons and different types of glial cells, such as astrocytes, microglia and oligodendrocytes. The relatively young field of "gliobiology" is thriving. Thanks to various technical innovations, it is now possible to address challenging biological questions on glial cells and unravel their multiple roles in brain function and dysfunction.

TITLE: De nouvelles techniques pour dévoiler le rôle des cellules gliales du cerveau. ABSTRACT: L'exécution des fonctions cérébrales requiert des interactions optimales entre les neurones et les différents types de cellules gliales (astrocytes, microglies et oligodendrocytes). Le domaine de la gliobiologie, qui s'intéresse aux cellules gliales, est en pleine expansion. Les innovations techniques permettent désormais d'aborder des questions biologiques complexes quant aux rôles de ces cellules dans le fonctionnement physiologique et pathologique du cerveau. Dans cette synthèse, nous décrivons comment certaines de ces avancées techniques nous ont permis d'en apprendre davantage sur les origines et les rôles fonctionnels des cellules gliales. Nous illustrons également comment ces techniques et les découvertes qui en ont découlé, peuvent être transposées en clinique et pourraient, dans un futur proche, offrir des nouvelles perspectives thérapeutiques.

Illuminating the immunopathology of SARS-CoV-2.

Over a remarkably short period of time, a great deal of knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been acquired, through the focused and cooperative effort of the international scientific community. Much has become known about how the immune response is coordinated to fight infection, and how it becomes dysregulated in severe disease. In this review, we take an in-depth look at the many immune features associated with the host response to SARS-CoV2, as well as those that appear to mark severe disease.

The future is now? Clinical and translational aspects of "Omics" technologies.

Big data has become a central part of medical research, as well as modern life generally. "Omics" technologies include genomics, proteomics, microbiomics and increasingly other omics. These have been driven by rapid advances in laboratory techniques and equipment. Crucially, improved information handling capabilities have allowed concepts such as artificial intelligence and machine learning to enter the research world. The COVID-19 pandemic has shown how quickly information can be generated and analyzed using such approaches, but also showed its limitations. This review will look at how "omics" has begun to be translated into clinical practice. While there appears almost limitless potential in using big data for "precision" or "personalized" medicine, the reality is that this remains largely aspirational. Oncology is the only field of medicine that is widely adopting such technologies, and even in this field uptake is irregular. There are practical and ethical reasons for this lack of translation of increasingly affordable techniques into the clinic. Undoubtedly, there will be increasing use of large data sets from traditional (e.g. tumor samples, patient genomics) and nontraditional (e.g. smartphone) sources. It is perhaps the greatest challenge of the health-care sector over the coming decade to integrate these resources in an effective, practical and ethical way.

Rapid nuclear magnetic resonance data acquisition with improved resolution and sensitivity for high-throughput metabolomic analysis.

Nuclear magnetic resonance (NMR)-based metabolomics has witnessed rapid advancements in recent years with the continuous development of new methods to enhance the sensitivity, resolution, and speed of data acquisition. Some of the approaches were earlier used for peptide and protein resonance assignments and have now been adapted to metabolomics. At the same time, new NMR methods involving novel data acquisition techniques, suited particularly for high-throughput analysis in metabolomics, have been developed. In this review, we focus on the different sampling strategies or data acquisition methods that have been developed in our laboratory and other groups to acquire NMR spectra rapidly with high sensitivity and resolution for metabolomics. In particular, we focus on the use of multiple receivers, phase modulation NMR spectroscopy, and fast-pulsing methods for identification and assignments of metabolites.

Analysis of steroid profiles by mass spectrometry: A new tool for exploring adrenal tumors?

The assay of multiple steroids by mass spectrometry coupled with chromatography, combined with data analysis using an artificial intelligence approach, has become more widely accessible in recent years. Multiple applications for this technology exist for the study of adrenocortical tumors. Taking advantage of the capacity of malignant cortical tumor secretion of non-bioactive precursors, it provides an additional diagnostic approach that can point to the nature of a tumor. These encouraging perspectives have been based to date only on pilot retrospective studies. However, this has changed in 2020 with the publication of data from the EURINE-ACT study. This very large prospective European study provided more nuanced evidence for the benefit of combining the measurement of a panel of steroids with essential imaging tools. This study also facilitated our understanding and provided more precise characterisation of autonomous steroid secretion, particularly in the case of sublinical cortisol-secreting adrenocortical adenomas. This article will focus on our current knowledge on the potential utility of mass spectrometry for diagnosis of both the nature of an adrenal tumors and their secretion.