scholarly journals From Targeted Quantification to Untargeted Metabolomics

2021 ◽  
Author(s):  
Veronica Lelli ◽  
Antonio Belardo ◽  
Anna Maria Timperio
Keyword(s):  
Biomarker Discovery ◽  
Biological Fluid ◽  
Biological Fluids ◽  
Disease Diagnosis ◽  
Untargeted Metabolomics ◽  
Metabolomic Analysis ◽  
Targeted Metabolomics ◽  
Two Phases ◽  
Technology Tool ◽  
New Biomarkers

Metabolomics is an emerging and rapidly evolving technology tool, which involves quantitative and qualitative metabolite assessments science. It offers tremendous promise for different applications in various fields such as medical, environmental, nutrition, and agricultural sciences. Metabolomic approach is based on global identification of a high number of metabolites present in a biological fluid. This allows to characterize the metabolic profile of a given condition and to identify which metabolites or metabolite patterns may be useful in the discrimination between different groups. The use of one mass spectrometry (MS) platform from targeted quantification to untargeted metabolomics will make more efficient workflows in many fields and should allow projects to be more easily undertaken and realized. Metabolomics can be divided into non-targeted and targeted. The first one can analyze metabolites derived from the organisms comprehensively and systematically, so it is an unbiased metabolomics analysis that can discover new biomarkers. Targeted metabolomics, on the other hand, is the study and analysis of specific metabolites. Both have their own advantages and disadvantages, and are often used in combination for discovery and accurate weight determination of differential metabolites, and allow in-depth research and analysis of subsequent metabolic molecular markers. Targeted and non-targeted metabolomics are involved in food identification, disease research, animal model verification, biomarker discovery, disease diagnosis, drug development, drug screening, drug evaluation, clinical plant metabolism and microbial metabolism research. The aim of this chapter is to highlight the versatility of metabolomic analysis due to both the enormous variety of samples and the no strict barriers between quantitative and qualitative analysis. For this purpose, two examples from our group will be considered. Using non-targeted metabolomics in opposite Antarctic cryptoendolytic communities exposed to the sun, we revealed specific adaptations. Instead, through the targeted metabolomics applied to the urine during childbirth, we identified a different distribution of specific metabolites and the metabolic differences allowed us to discriminate between the two phases of labor, highlighting the metabolites most involved in the discrimination. The choice of these two approaches is to highlight that metabolomic analysis can be applied to any sample, even physiologically and metabolomically very distant, as can be microorganisms living on Antarctic rocks and biological fluids such as urine.

scholarly journals Glycans as Biomarkers: Status and Perspectives

2011 ◽  
Vol 30 (3) ◽  
pp. 213-223 ◽  
Author(s):  
Miroslava Janković
Keyword(s):  
Large Scale ◽  
Biomarker Discovery ◽  
High Sensitivity ◽  
Disease Diagnosis ◽  
Protein Glycosylation ◽  
Post Translational Modification ◽  
Different Types ◽  
Progression Of Disease ◽  
New Biomarkers ◽  
Selection Of

Glycans as Biomarkers: Status and PerspectivesProtein glycosylation is a ubiquitous and complex co- and post-translational modification leading to glycan formation, i.e. oligosaccharide chains covalently attached to peptide backbones. The significance of changes in glycosylation for the beginning, progress and outcome of different human diseases is widely recognized. Thus, glycans are considered as unique structures to diagnose, predict susceptibility to and monitor the progression of disease. In the »omics« era, the glycome, a glycan analogue of the proteome and genome, holds considerable promise as a source of new biomarkers. In the design of a strategy for biomarker discovery, new principles and platforms for the analysis of relatively small amounts of numerous glycoproteins are needed. Emerging glycomics technologies comprising different types of mass spectrometry and affinity-based arrays are next in line to deliver new analytical procedures in the field of biomarkers. Screening different types of glycomolecules, selection of differentially expressed components, their enrichment and purification or identification are the most challenging parts of experimental and clinical glycoproteomics. This requires large-scale technologies enabling high sensitivity, proper standardization and validation of the methods to be used. Further progress in the field of applied glycoscience requires an integrated systematic approach in order to explore properly all opportunities for disease diagnosis.

Untargeted metabolomics for plasma biomarker discovery for early chronic kidney disease diagnosis in pediatric patients using LC-QTOF-MS

The Analyst ◽  
2018 ◽  
Vol 143 (18) ◽  
pp. 4448-4458 ◽  
Author(s):  
S. Benito ◽  
A. Sánchez-Ortega ◽  
N. Unceta ◽  
F. Andrade ◽  
L. Aldámiz-Echevarria ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Pediatric Patients ◽  
Biomarker Discovery ◽  
Disease Diagnosis ◽  
Clinical Syndrome ◽  
Kidney Damage ◽  
Untargeted Metabolomics ◽  
Plasma Biomarker ◽  
Over Time

Pediatric chronic kidney disease (CKD) is a clinical syndrome characterized by renal hypofunction occurring due to gradual and irreversible kidney damage that can further progress over time.

scholarly journals Untargeted Metabolomic Analysis Combined With Multivariate Statistics Reveal Distinct Metabolic Changes in GPR40 Agonist-Treated Animals Related to Bile Acid Metabolism

2021 ◽  
Vol 7 ◽  
Author(s):  
Hannes Doerfler ◽  
Dana-Adriana Botesteanu ◽  
Stefan Blech ◽  
Ralf Laux
Keyword(s):  
Bile Acid ◽  
Multivariate Statistics ◽  
Biomarker Discovery ◽  
Liver Toxicity ◽  
Untargeted Metabolomics ◽  
Bile Acid Metabolism ◽  
Metabolomic Analysis ◽  
Drug Induced ◽  
Metabolomics Data

Metabolomics has been increasingly applied to biomarker discovery, as untargeted metabolic profiling represents a powerful exploratory tool for identifying causal links between biomarkers and disease phenotypes. In the present work, we used untargeted metabolomics to investigate plasma specimens of rats, dogs, and mice treated with small-molecule drugs designed for improved glycemic control of type 2 diabetes mellitus patients via activation of GPR40. The in vivo pharmacology of GPR40 is not yet fully understood. Compounds targeting this receptor have been found to induce drug-induced liver injury (DILI). Metabolomic analysis facilitating an integrated UPLC-TWIMS-HRMS platform was used to detect metabolic differences between treated and non-treated animals within two 4-week toxicity studies in rat and dog, and one 2-week toxicity study in mouse. Multivariate statistics of untargeted metabolomics data subsequently revealed the presence of several significantly upregulated endogenous compounds in the treated animals whose plasma level is known to be affected during DILI. A specific bile acid metabolite useful as endogenous probe for drug–drug interaction studies was identified (chenodeoxycholic acid-24 glucuronide), as well as a metabolic precursor indicative of acidic bile acid biosynthesis (7α-hydroxy-3-oxo-4-cholestenoic acid). These results correlate with typical liver toxicity parameters on the individual level.

From “Clinical Proteomics” to “Clinical Chemistry Proteomics”: considerations using quantitative mass-spectrometry as a model approach

2012 ◽  
Vol 50 (2) ◽  
Author(s):  
Sylvain Lehmann ◽  
Pauline Poinot ◽  
Laurent Tiers ◽  
Christophe Junot ◽  
François Becher ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Biomarker Discovery ◽  
Clinical Chemistry ◽  
Biological Fluids ◽  
Clinical Proteomics ◽  
Detection Methods ◽  
Patient Treatment ◽  
Quantitative Detection ◽  
New Biomarkers

AbstractClinical Proteomics biomarker discovery programs lead to the selection of putative new biomarkers of human pathologies. Following an initial discovery phase, validation of these candidates in larger populations is a major task that recently started relying upon the use of mass spectrometry approaches, especially in cases where classical immune-detection methods were lacking. Thanks to highly sensitive spectrometers, adapted measurement methods like selective reaction monitoring (SRM) and various pre-fractionation methods, the quantitative detection of protein/peptide biomarkers in low concentrations is now feasible from complex biological fluids. This possibility leads to the use of similar methodologies in clinical biology laboratories, within a new proteomic field that we shall name “Clinical Chemistry Proteomics” (CCP). Such evolution of Clinical Proteomics adds important constraints with regards to the in vitro diagnostic (IVD) application. As measured values of analytes will be used to diagnose, follow-up and adapt patient treatment on a routine basis; medical utility, robustness, reference materials and clinical feasibility are among the new issues of CCP to consider.

scholarly journals EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Agnes T. Reiner ◽  
Sisareuth Tan ◽  
Christiane Agreiter ◽  
Katharina Auer ◽  
Anna Bachmayr-Heyda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Biomarker Discovery ◽  
Signal To Noise Ratio ◽  
Biological Fluids ◽  
Annexin V ◽  
Extracellular Vesicle ◽  
Lipid Binding ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
New Biomarkers

High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo. This approach circumvents the low signal-to-noise ratio when using biological fluids for biomarker discovery and the issue of contamination by large non-EV complexes. We isolated and analyzed three distinct EV populations from the ascites of patients with ovarian cancer or cirrhosis and observed that Annexin V-binding EVs have higher levels of matrix metalloproteinase 9 in malignant compared to portal-hypertensive ascites. As this protein was not detected in other EV populations, this study validates our approach of using different EV types for optimal biomarker discovery. Furthermore, MMP9 in Annexin V-binding EVs could be a HGSOC biomarker with enhanced specificity, because its identification requires detection of two distinct components, that is, lipid and protein.

Separation of Extracellular Vesicles by DNA-Directed Immunocapturing Followed by Enzymatic Release

2020 ◽  
Author(s):  
Dario Brambilla ◽  
Laura Sola ◽  
Elisa Chiodi ◽  
Natasa Zarovni ◽  
Diogo Fortunato ◽  
...  
Keyword(s):  
Cell Culture ◽  
Extracellular Vesicles ◽  
Culture Media ◽  
Biological Fluids ◽  
Imaging Techniques ◽  
Cell Communication ◽  
Disease Diagnosis ◽  
Cell Culture Supernatant ◽  
Transmission Electron ◽  
Downstream Analysis

Extracellular vesicles (EVs) have attracted great interest among researchers due to their role in cell-cell communication, disease diagnosis, and drug delivery. In spite of their potential in the medical field, there is no consensus on the best method for separating microvesicles from cell culture supernatant and complex biological fluids. Obtaining a good recovery yield and preserving physical characteristics is critical for the diagnostic and therapeutic use of EVs. The separation is made complex by the fact that blood and cell culture media, contain a large number of nanoparticles in the same size range. Methods that exploit immunoaffinity capture provide high purity samples and overcome the issues of currently used separation methods. However, the release of captured nanovesicles requires harsh conditions that hinder their use in certain types of downstream analysis. Herein, a novel capture and release approach for small extracellular vesicles (sEVs), based on DNAdirected immobilization of antiCD63 antibody is presented. The flexible DNAlinker increases the capture efficiency and allows releasing of EVs by exploiting the endonucleasic activity of DNAse I. This separation protocol works under mild conditions, enabling the release of intact vesicles that can be successfully analyzed by imaging techniques. In this article sEVs recovered from plasma were characterized by established techniques for EVs analysis including nanoparticle tracking and transmission electron microscopy.<br>

scholarly journals Metabolic Evaluation of Urine from Patients Diagnosed with High Grade (HG) Bladder Cancer by SPME-LC-MS Method

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  
Keyword(s):  
Thin Film ◽  
Bladder Cancer ◽  
High Performance ◽  
Biomarker Discovery ◽  
Solid Phase ◽  
Biological Fluids ◽  
Reversed Phase ◽  
Control Group ◽  
Metabolic Evaluation ◽  
Metabolomic Profiling

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.

scholarly journals Current Status and Future Perspectives about Molecular Biomarkers of Nasopharyngeal Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3490
Author(s):  
Pui Yan Siak ◽  
Alan Soo-Beng Khoo ◽  
Chee Onn Leong ◽  
Boon-Peng Hoh ◽  
Shiau-Chuen Cheah
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Biomarker Discovery ◽  
Southern China ◽  
Disease Diagnosis ◽  
Late Presentation ◽  
Dietary Factors ◽  
Current Status ◽  
Complex Nature ◽  
Epstein Barr Virus Infection ◽  
Potential Biomarker

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that shows a remarkable ethnic and geographical distribution. It is one of the major public health problems in some countries, especially Southern China and Southeast Asia, but rare in most Western countries. Multifactorial interactions such as Epstein–Barr virus infection, individual’s genetic susceptibility, as well as environmental and dietary factors may facilitate the pathogenesis of this malignancy. Late presentation and the complex nature of the disease have led it to become a major cause of mortality. Therefore, an effective, sensitive, and specific molecular biomarker is urgently needed for early disease diagnosis, prognosis, and prediction of metastasis and recurrence after treatment. In this review, we discuss the recent research status of potential biomarker discovery and the problems that need to be explored further for better NPC management. By studying the aberrant pattern of these candidate biomarkers that promote NPC development and progression, we are able to understand the complexity of this malignancy better, hence positing our stands better towards strategies that may provide a way forward to the discovery of more reliable and specific biomarkers for diagnosis and targeted therapeutic development.

scholarly journals Next-Generation Biomarkers for Cholangiocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3222
Author(s):  
Pedro M. Rodrigues ◽  
Arndt Vogel ◽  
Marco Arrese ◽  
Domingo C. Balderramo ◽  
Juan W. Valle ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Tumor Development ◽  
Predictive Biomarkers ◽  
Disease Diagnosis ◽  
Future Research ◽  
Tumor Biopsy ◽  
Non Invasive ◽  
Tumor Stages ◽  
At Risk Populations ◽  
Early Tumor

The increasing mortality rates of cholangiocarcinoma (CCA) registered during the last decades are, at least in part, a result of the lack of accurate non-invasive biomarkers for early disease diagnosis, making the identification of patients who might benefit from potentially curative approaches (i.e., surgery) extremely challenging. The obscure CCA pathogenesis and associated etiological factors, as well as the lack of symptoms in patients with early tumor stages, highly compromises CCA identification and to predict tumor development in at-risk populations. Currently, CCA diagnosis is accomplished by the combination of clinical/biochemical features, radiological imaging and non-specific serum tumor biomarkers, although a tumor biopsy is still needed to confirm disease diagnosis. Furthermore, prognostic and predictive biomarkers are still lacking and urgently needed. During the recent years, high-throughput omics-based approaches have identified novel circulating biomarkers (diagnostic and prognostic) that might be included in large, international validation studies in the near future. In this review, we summarize and discuss the most recent advances in the field of biomarker discovery in CCA, providing new insights and future research directions.

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