Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.3
4.1
Journals
Metabolites
Special Issues
Clinical Metabolomics
share announcement

Clinical Metabolomics

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 May 2018) | Viewed by 46175

Special Issue Editor

Assoc. Prof. Vidya Velagapudi

E-Mail Website
Guest Editor
Head of Metabolomics Unit, Technology Centre, Institute for Molecular Medicine Finland FIMM, University of Helsinki, P.O Box-20, 00014 Helsinki, Finland
Interests: clinical metabolomics and lipidomics; systems medicine (metabolic syndromes); fluxomics and metabolic network analysis

Special Issue Information

Dear Colleagues,

Metabolomics aims at the comprehensive quantitative analysis of all metabolites in a biological system, as well as their dynamics, composition, interactions, and responses to interventions or a specific physiological state. Unlike most compound-specific analyses of traditional clinical chemistry, metabolomics systematically permits studies of the metabolome, and offers deeper insights into deciphering biological processes. Systematic metabolomics analysis at the right time-points provides new molecular insights that assist in the elucidation of metabolic dysregulation underlying disease development, which improves risk prediction—a crucial step for the advancement of prevention and treatment strategies. In addition, the metabolomics approach correlates broad biochemical changes with health and disease states, and advanced statistical metabolic modeling allows the identification of biomarkers with good predictive power. This Special Issue of Metabolites is dedicated to Clinical Metabolomics. The aims and scope of this Special Issue will include, but are not limited to, in-born errors of metabolism, biomarker discovery, metabolic syndromes, systems biology, and personalised and translational medicine.

Assoc. Prof. Vidya Velagapudi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • metabolomics
  • lipidomics
  • biomarkers
  • systems biology
  • metabolic disorders
  • patient stratification
  • translational medicine

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

17 pages, 21096 KiB  
Article
LC-HRMS Metabolomics for Untargeted Diagnostic Screening in Clinical Laboratories: A Feasibility Study
by Bertrand Rochat, Rayane Mohamed and Pierre-Edouard Sottas
Metabolites 2018, 8(2), 39; https://doi.org/10.3390/metabo8020039 - 15 Jun 2018
Cited by 10 | Viewed by 5702
Abstract
Today’s high-resolution mass spectrometers (HRMS) allow bioanalysts to perform untargeted/global determinations that can reveal unexpected compounds or concentrations in a patient’s sample. This could be performed for preliminary diagnosis attempts when usual diagnostic processes and targeted determinations fail. We have evaluated an untargeted [...] Read more.
Today’s high-resolution mass spectrometers (HRMS) allow bioanalysts to perform untargeted/global determinations that can reveal unexpected compounds or concentrations in a patient’s sample. This could be performed for preliminary diagnosis attempts when usual diagnostic processes and targeted determinations fail. We have evaluated an untargeted diagnostic screening (UDS) procedure. UDS is a metabolome analysis that compares one sample (e.g., a patient) with control samples (a healthy population). Using liquid chromatography (LC)-HRMS full-scan analysis of human serum extracts and unsupervised data treatment, we have compared individual samples that were spiked with one xenobiotic or a higher level of one endogenous compound with control samples. After the use of different filters that drastically reduced the number of metabolites detected, the spiked compound was eventually revealed in each test sample and ranked. The proposed UDS procedure appears feasible and reliable to reveal unexpected xenobiotics (toxicology) or higher concentrations of endogenous metabolites. HRMS-based untargeted approaches could be useful as preliminary diagnostic screening when canonical processes do not reveal disease etiology nor establish a clear diagnosis and could reduce misdiagnosis. On the other hand, the risk of overdiagnosis of this approach should be reduced with mandatory biomedical interpretation of the patient’s UDS results and with confirmatory targeted and quantitative determinations. Full article
(This article belongs to the Special Issue Clinical Metabolomics)
►▼ Show Figures

Graphical abstract

12 pages, 1677 KiB  
Article
Global Metabolomics of the Placenta Reveals Distinct Metabolic Profiles between Maternal and Fetal Placental Tissues Following Delivery in Non-Labored Women
by Jacquelyn M. Walejko, Anushka Chelliah, Maureen Keller-Wood, Anthony Gregg and Arthur S. Edison
Metabolites 2018, 8(1), 10; https://doi.org/10.3390/metabo8010010 - 23 Jan 2018
Cited by 35 | Viewed by 6334
Abstract
We evaluated the metabolic alterations in maternal and fetal placental tissues from non-labored women undergoing cesarean section using samples collected from 5 min to 24 h following delivery. Using 1H-NMR, we identified 14 metabolites that significantly differed between maternal and fetal placental [...] Read more.
We evaluated the metabolic alterations in maternal and fetal placental tissues from non-labored women undergoing cesarean section using samples collected from 5 min to 24 h following delivery. Using 1H-NMR, we identified 14 metabolites that significantly differed between maternal and fetal placental tissues (FDR-corrected p-value < 0.05), with 12 metabolites elevated in the maternal tissue, reflecting the flux of these metabolites from mother to fetus. In the maternal tissue, 4 metabolites were significantly altered at 15 min, 10 metabolites at 30 min, and 16 metabolites at 1 h postdelivery, while 11 metabolites remained stable over 24 h. In contrast, in the fetal placenta tissue, 1 metabolite was significantly altered at 15 min, 2 metabolites at 30 min, and 4 metabolites at 1 h postdelivery, while 22 metabolites remained stable over 24 h. Our study provides information on the metabolic profiles of maternal and fetal placental tissues delivered by cesarean section and reveals that there are different metabolic alterations in the maternal and fetal tissues of the placenta following delivery. Full article
(This article belongs to the Special Issue Clinical Metabolomics)
►▼ Show Figures

Graphical abstract

13 pages, 2471 KiB  
Article
Impact of Prolonged Blood Incubation and Extended Serum Storage at Room Temperature on the Human Serum Metabolome
by Beate Kamlage, Sebastian Neuber, Bianca Bethan, Sandra González Maldonado, Antje Wagner-Golbs, Erik Peter, Oliver Schmitz and Philipp Schatz
Metabolites 2018, 8(1), 6; https://doi.org/10.3390/metabo8010006 - 13 Jan 2018
Cited by 30 | Viewed by 6605
Abstract
Metabolomics is a powerful technology with broad applications in life science that, like other -omics approaches, requires high-quality samples to achieve reliable results and ensure reproducibility. Therefore, along with quality assurance, methods to assess sample quality regarding pre-analytical confounders are urgently needed. In [...] Read more.
Metabolomics is a powerful technology with broad applications in life science that, like other -omics approaches, requires high-quality samples to achieve reliable results and ensure reproducibility. Therefore, along with quality assurance, methods to assess sample quality regarding pre-analytical confounders are urgently needed. In this study, we analyzed the response of the human serum metabolome to pre-analytical variations comprising prolonged blood incubation and extended serum storage at room temperature by using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) -based metabolomics. We found that the prolonged incubation of blood results in a statistically significant 20% increase and 4% decrease of 225 tested serum metabolites. Extended serum storage affected 21% of the analyzed metabolites (14% increased, 7% decreased). Amino acids and nucleobases showed the highest percentage of changed metabolites in both confounding conditions, whereas lipids were remarkably stable. Interestingly, the amounts of taurine and O-phosphoethanolamine, which have both been discussed as biomarkers for various diseases, were 1.8- and 2.9-fold increased after 6 h of blood incubation. Since we found that both are more stable in ethylenediaminetetraacetic acid (EDTA) blood, EDTA plasma should be the preferred metabolomics matrix. Full article
(This article belongs to the Special Issue Clinical Metabolomics)
►▼ Show Figures

Figure 1

3535 KiB  
Article
Integrated Metabolomics Assessment of Human Dried Blood Spots and Urine Strips
by Jeremy Drolet, Vladimir Tolstikov, Brian A. Williams, Bennett P. Greenwood, Collin Hill, Vivek K. Vishnudas, Rangaprasad Sarangarajan, Niven R. Narain and Michael A. Kiebish
Metabolites 2017, 7(3), 35; https://doi.org/10.3390/metabo7030035 - 15 Jul 2017
Cited by 41 | Viewed by 8173
Abstract
(1) Background: Interest in the application of metabolomics toward clinical diagnostics development and population health monitoring has grown significantly in recent years. In spite of several advances in analytical and computational tools, obtaining a sufficient number of samples from patients remains an obstacle. [...] Read more.
(1) Background: Interest in the application of metabolomics toward clinical diagnostics development and population health monitoring has grown significantly in recent years. In spite of several advances in analytical and computational tools, obtaining a sufficient number of samples from patients remains an obstacle. The dried blood spot (DBS) and dried urine strip (DUS) methodologies are a minimally invasive sample collection method allowing for the relative simplicity of sample collection and minimal cost. (2) Methods: In the current report, we compared results of targeted metabolomics analyses of four types of human blood sample collection methods (with and without DBS) and two types of urine sample collection (DUS and urine) across several parameters including the metabolite coverage of each matrix and the sample stability for DBS/DUS using commercially available Whatman 903TM paper. The DBS/DUS metabolomics protocols were further applied to examine the temporal metabolite level fluctuations within hours and days of sample collection. (3) Results: Several hundred polar metabolites were monitored using DBS/DUS. Temporal analysis of the polar metabolites at various times of the day and across days identified several species that fluctuate as a function of day and time. In addition, a subset of metabolites were identified to be significantly altered across hours within a day and within successive days of the week. (4) Conclusion: A comprehensive DBS/DUS metabolomics protocol was developed for human blood and urine analyses. The described methodology demonstrates the potential for enabling patients to contribute to the expanding bioanalytical demands of precision medicine and population health studies. Full article
(This article belongs to the Special Issue Clinical Metabolomics)
►▼ Show Figures

Figure 1

1106 KiB  
Article
Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps
by Lu Deng, David Chang, Rae R. Foshaug, Roman Eisner, Victor K. Tso, David S. Wishart and Richard N. Fedorak
Metabolites 2017, 7(3), 32; https://doi.org/10.3390/metabo7030032 - 22 Jun 2017
Cited by 29 | Viewed by 6122
Abstract
Background: Colorectal cancer is one of the leading causes of cancer deaths worldwide. The detection and removal of the precursors to colorectal cancer, adenomatous polyps, is the key for screening. The aim of this study was to develop a clinically scalable (high throughput, [...] Read more.
Background: Colorectal cancer is one of the leading causes of cancer deaths worldwide. The detection and removal of the precursors to colorectal cancer, adenomatous polyps, is the key for screening. The aim of this study was to develop a clinically scalable (high throughput, low cost, and high sensitivity) mass spectrometry (MS)-based urine metabolomic test for the detection of adenomatous polyps. Methods: Prospective urine and stool samples were collected from 685 participants enrolled in a colorectal cancer screening program to undergo colonoscopy examination. Statistical analysis was performed on 69 urine metabolites measured by one-dimensional nuclear magnetic resonance spectroscopy to identify key metabolites. A targeted MS assay was then developed to quantify the key metabolites in urine. A MS-based urine metabolomic diagnostic test for adenomatous polyps was established using 67% samples (un-blinded training set) and validated using the remaining 33% samples (blinded testing set). Results: The MS-based urine metabolomic test identifies patients with colonic adenomatous polyps with an AUC of 0.692, outperforming the NMR based predictor with an AUC of 0.670. Conclusion: Here we describe a clinically scalable MS-based urine metabolomic test that identifies patients with adenomatous polyps at a higher level of sensitivity (86%) over current fecal-based tests (<18%). Full article
(This article belongs to the Special Issue Clinical Metabolomics)
►▼ Show Figures

Figure 1

1688 KiB  
Article
Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo
by Brian C. Jensen, Traci L. Parry, Wei Huang, Amro Ilaiwy, James R. Bain, Michael J. Muehlbauer, Sara K. O’Neal, Cam Patterson, Gary L. Johnson and Monte S. Willis
Metabolites 2017, 7(3), 31; https://doi.org/10.3390/metabo7030031 - 22 Jun 2017
Cited by 17 | Viewed by 6637
Abstract
Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor [...] Read more.
Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR), whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR).TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities. Cardiotoxicity is very rare in patients treated with erlotinib, but considerably more common after sunitinib treatment. We hypothesized that the deleterious effects of TKIs on the heart were related to their impact on cardiac metabolism. Methods: Female FVB/N mice (10/group) were treated with therapeutic doses of sunitinib (40 mg/kg), erlotinib (50 mg/kg), or vehicle daily for two weeks. Echocardiographic assessment of the heart in vivo was performed at baseline and on Day 14. Heart, skeletal muscle, liver and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Results: Compared to vehicle-treated controls, sunitinib-treated mice had significant decreases in systolic function, whereas erlotinib-treated mice did not. Non-targeted metabolomics analysis of heart identified significant decreases in docosahexaenoic acid (DHA), arachidonic acid (AA)/ eicosapentaenoic acid (EPA), O-phosphocolamine, and 6-hydroxynicotinic acid after sunitinib treatment. DHA was significantly decreased in skeletal muscle (quadriceps femoris), while elevated cholesterol was identified in liver and elevated ethanolamine identified in serum. In contrast, erlotinib affected only one metabolite (spermidine significantly increased). Conclusions: Mice treated with sunitinib exhibited systolic dysfunction within two weeks, with significantly lower heart and skeletal muscle levels of long chain omega-3 fatty acids docosahexaenoic acid (DHA), arachidonic acid (AA)/eicosapentaenoic acid (EPA) and increased serum O-phosphocholine phospholipid. This is the first link between sunitinib-induced cardiotoxicity and depletion of the polyunsaturated fatty acids (PUFAs) and inflammatory mediators DHA and AA/EPA in the heart. These compounds have important roles in maintaining mitochondrial function, and their loss may contribute to cardiac dysfunction. Full article
(This article belongs to the Special Issue Clinical Metabolomics)
►▼ Show Figures

Figure 1

Review

Jump to: Research

12 pages, 230 KiB  
Review
Study of the Serum Metabolomic Profile in Nonalcoholic Fatty Liver Disease: Research and Clinical Perspectives
by Stefano Gitto, Filippo Schepis, Pietro Andreone and Erica Villa
Metabolites 2018, 8(1), 17; https://doi.org/10.3390/metabo8010017 - 24 Feb 2018
Cited by 33 | Viewed by 5350
Abstract
In recent years, metabolomics has attracted great scientific attention. The metabolomics methodology might permit a view into transitional phases between healthy liver and nonalcoholic steatohepatitis. Metabolomics can help to analyze the metabolic alterations that play a main role in the progression of nonalcoholic [...] Read more.
In recent years, metabolomics has attracted great scientific attention. The metabolomics methodology might permit a view into transitional phases between healthy liver and nonalcoholic steatohepatitis. Metabolomics can help to analyze the metabolic alterations that play a main role in the progression of nonalcoholic steatohepatitis. Lipid, glucose, amino acid, and bile acid metabolism should be widely studied to understand the complex pathogenesis of nonalcoholic steatohepatitis. The discovery of new biomarkers would be important for diagnosis and staging of liver disease as well as for the assessment of efficacy of new drugs. Here, we review the metabolomics data regarding nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. We analyzed the main studies regarding the application of metabolomics methodology in the complex context of nonalcoholic steatohepatitis, trying to create a bridge from the basic to the clinical aspects. Full article
(This article belongs to the Special Issue Clinical Metabolomics)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop