Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis
Publication Date
October 27, 2015
Journal
PLOS Neglected Tropical Diseases
Authors
Sabrina D. Lamour, Maria Gomez Romero, Panagiotis A. Vorkas, Vincent P. Alibu, et al
Volume
9
Issue
10
Pages
e0004200
DOI
https://dx.plos.org/10.1371/journal.pntd.0004200
Publisher URL
http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0004200
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/26505639
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624234
Europe PMC
http://europepmc.org/abstract/MED/26505639
Web of Science
000364459600079
Scopus
84959195210
Mendeley
http://www.mendeley.com/research/discovery-infection-associated-metabolic-markers-human-african-trypanosomiasis
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2381917"], "description"=>"<p>S-plots of O-PLS-DA model for plasma lipid profiling UPLC-MS features detected in ESI+ mode (A) and ESI- mode (B), whereby each circle represents one feature with a unique combination of m/z and retention time values. Discriminatory features selected surpassed p[<a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004200#pntd.0004200.ref001\" target=\"_blank\">1</a>] and p(corr)[<a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004200#pntd.0004200.ref001\" target=\"_blank\">1</a>] threshold criteria, highlighted in red boxes (see <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004200#sec002\" target=\"_blank\">Methods</a>). See <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004200#pntd.0004200.s001\" target=\"_blank\">S1 Fig</a> for corresponding scores plots. Integrals of features highlighted in the S-plots are shown as bar-chart showing mean averages ± standard error of the mean, for both ESI+ (C) and ESI- (D). Patients levels are shown in red (<i>n</i> = 16) and controls in dark grey (<i>n</i> = 14). Significant differences, as measured via Welch T-test with multiple test correction, are labelled with asterisks, where *** <i>p</i><0.001. Abbreviations: A.U., arbitrary units; LysoPC, lysophosphatidylcholine; PC, phosphatidylcholine.</p>", "links"=>[], "tags"=>["Trypanosoma brucei rhodesiense", "disease metabolite profile", "host response", "Animal models", "prognostic markers", "rodent infection", "Infection Associated Metabolic Markers", "mass spectrometry", "metabolite markers", "T.b.rhodesiense HAT patients", "acid profile markers", "immunodiagnostic approaches", "trypanosome infections", "1 H", "nmr", "pathogenetic mechanisms", "37 lipid markers", "optimise treatment", "HAT patients", "metabolite profiles", "Trypanosomiasis Human"], "article_id"=>1586637, "categories"=>["Uncategorised"], "users"=>["Sabrina D. Lamour", "Maria Gomez-Romero", "Panagiotis A. Vorkas", "Vincent P. Alibu", "Jasmina Saric", "Elaine Holmes", "Jeremy M. Sternberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0004200.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_in_HAT_patients_display_different_lipid_profiles_compared_with_controls_/1586637", "title"=>"Plasma in HAT patients display different lipid profiles compared with controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-27 03:58:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/2381915"], "description"=>"<p>Bar-charts show relative levels of plasma metabolites that were significantly altered between patients (shown in red, <i>n</i> = 45) and controls (shown in grey, <i>n</i> = 21), as measured by <sup>1</sup>H NMR spectroscopy. (A) Metabolites higher in patients than controls. (B). Metabolites lower in patients than controls. Bars represent group mean average with standard error of the mean as error bars. Significance measured via Welch T-test with multiple test correction, shown as asterisks; * <i>p</i><0.05, ** <i>p</i><0.01, *** <i>p</i><0.001. A.U., arbitrary units; NAG, <i>N</i>-acetyl glycoproteins.</p>", "links"=>[], "tags"=>["Trypanosoma brucei rhodesiense", "disease metabolite profile", "host response", "Animal models", "prognostic markers", "rodent infection", "Infection Associated Metabolic Markers", "mass spectrometry", "metabolite markers", "T.b.rhodesiense HAT patients", "acid profile markers", "immunodiagnostic approaches", "trypanosome infections", "1 H", "nmr", "pathogenetic mechanisms", "37 lipid markers", "optimise treatment", "HAT patients", "metabolite profiles", "Trypanosomiasis Human"], "article_id"=>1586635, "categories"=>["Uncategorised"], "users"=>["Sabrina D. Lamour", "Maria Gomez-Romero", "Panagiotis A. Vorkas", "Vincent P. Alibu", "Jasmina Saric", "Elaine Holmes", "Jeremy M. Sternberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0004200.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differences_in_plasma_metabolites_between_HAT_patients_and_controls_detected_by_NMR_/1586635", "title"=>"Differences in plasma metabolites between HAT patients and controls detected by NMR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-27 03:58:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/2381922", "https://ndownloader.figshare.com/files/2381923", "https://ndownloader.figshare.com/files/2381924", "https://ndownloader.figshare.com/files/2381925", "https://ndownloader.figshare.com/files/2381926", "https://ndownloader.figshare.com/files/2381927", "https://ndownloader.figshare.com/files/2381928"], "description"=>"<div><p>Human African trypanosomiasis (HAT) remains a major neglected tropical disease in Sub-Saharan Africa. As clinical symptoms are usually non-specific, new diagnostic and prognostic markers are urgently needed to enhance the number of identified cases and optimise treatment. This is particularly important for disease caused by <i>Trypanosoma brucei rhodesiense</i>, where indirect immunodiagnostic approaches have to date been unsuccessful. We have conducted global metabolic profiling of plasma from <i>T</i>.<i>b</i>.<i>rhodesiense</i> HAT patients and endemic controls, using <sup>1</sup>H nuclear magnetic resonance (NMR) spectroscopy and ultra-performance liquid chromatography, coupled with mass spectrometry (UPLC-MS) and identified differences in the lipid, amino acid and metabolite profiles. Altogether 16 significantly disease discriminatory metabolite markers were found using NMR, and a further 37 lipid markers via UPLC-MS. These included significantly higher levels of phenylalanine, formate, creatinine, <i>N</i>-acetylated glycoprotein and triglycerides in patients relative to controls. HAT patients also displayed lower concentrations of histidine, sphingomyelins, lysophosphatidylcholines, and several polyunsaturated phosphatidylcholines. While the disease metabolite profile was partially consistent with previous data published in experimental rodent infection, we also found unique lipid and amino acid profile markers highlighting subtle but important differences between the host response to trypanosome infections between animal models and natural human infections. Our results demonstrate the potential of metabolic profiling in the identification of novel diagnostic biomarkers and the elucidation of pathogenetic mechanisms in this disease.</p></div>", "links"=>[], "tags"=>["Trypanosoma brucei rhodesiense", "disease metabolite profile", "host response", "Animal models", "prognostic markers", "rodent infection", "Infection Associated Metabolic Markers", "mass spectrometry", "metabolite markers", "T.b.rhodesiense HAT patients", "acid profile markers", "immunodiagnostic approaches", "trypanosome infections", "1 H", "nmr", "pathogenetic mechanisms", "37 lipid markers", "optimise treatment", "HAT patients", "metabolite profiles", "Trypanosomiasis Human"], "article_id"=>1586641, "categories"=>["Uncategorised"], "users"=>["Sabrina D. Lamour", "Maria Gomez-Romero", "Panagiotis A. Vorkas", "Vincent P. Alibu", "Jasmina Saric", "Elaine Holmes", "Jeremy M. Sternberg"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0004200.s001", "https://dx.doi.org/10.1371/journal.pntd.0004200.s002", "https://dx.doi.org/10.1371/journal.pntd.0004200.s003", "https://dx.doi.org/10.1371/journal.pntd.0004200.s004", "https://dx.doi.org/10.1371/journal.pntd.0004200.s005", "https://dx.doi.org/10.1371/journal.pntd.0004200.s006", "https://dx.doi.org/10.1371/journal.pntd.0004200.s007"], "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Discovery_of_Infection_Associated_Metabolic_Markers_in_Human_African_Trypanosomiasis_/1586641", "title"=>"Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-10-27 03:58:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/2381914"], "description"=>"<p>PCA model (A) and O-PLS-DA model (B) score plots of plasma <sup>1</sup>H NMR spectra across HAT patients and controls. Each circle represents a spectra from one sample, whereby patients are presented in red (<i>n</i> = 45) and controls in dark grey (<i>n</i> = 21). Abbreviations: R<sup>2</sup>X, model fit parameter for variation in spectral data; R<sup>2</sup>Y, model fit parameter for variation in classifier data (for O-PLS-DA); Q<sup>2</sup>, model predictive parameter for spectral data in PCA (Q<sup>2</sup>X) and for classifier data in O-PLS-DA (Q<sup>2</sup>Y). Individual component contribution of R<sup>2</sup>X are shown on the axes as percentage.</p>", "links"=>[], "tags"=>["Trypanosoma brucei rhodesiense", "disease metabolite profile", "host response", "Animal models", "prognostic markers", "rodent infection", "Infection Associated Metabolic Markers", "mass spectrometry", "metabolite markers", "T.b.rhodesiense HAT patients", "acid profile markers", "immunodiagnostic approaches", "trypanosome infections", "1 H", "nmr", "pathogenetic mechanisms", "37 lipid markers", "optimise treatment", "HAT patients", "metabolite profiles", "Trypanosomiasis Human"], "article_id"=>1586634, "categories"=>["Uncategorised"], "users"=>["Sabrina D. Lamour", "Maria Gomez-Romero", "Panagiotis A. Vorkas", "Vincent P. Alibu", "Jasmina Saric", "Elaine Holmes", "Jeremy M. Sternberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0004200.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_in_HAT_patients_display_different_1_H_NMR_metabolic_profiles_compared_with_controls_/1586634", "title"=>"Plasma in HAT patients display different <sup>1</sup>H NMR metabolic profiles compared with controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-27 03:58:11"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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