The human cerebrospinal fluid metabolome

Wishart, David S.; Lewis, Michael; Morrissey, Joshua A.; Flegel, M.D.; Jeroncic, Kevin; Xiong, Yeping; Cheng, Dongping; Eisner, Roman; Gautam, Bijaya; Tzur, Dan; Sawhney, Summit; Bamforth, Fiona; Greiner, Russ; Li, Liang

doi:10.1016/j.jchromb.2008.05.001

Cited by 316 publications

(282 citation statements)

References 31 publications

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“…This, in contrast to GC-MS for which metabolites can only be quantified when either internal standards or calibration curves for each metabolite are used, which is practically not feasible; therefore, this method, similar to many other non-targeted methods, is used to measure relative differences in metabolite concentrations between groups or individuals. The absolute concentrations determined by LC-MS/MS and NMR agree well with values reported in literature (13,(33)(34)(35). For example, comparison of the concentrations of metabolites detected by NMR with values determined by Wishart et al (13) and literature values referred to in their paper show that in most cases the values fall within the same concentration range (see Supplementary Material).…”

Section: Discussionsupporting

confidence: 87%

“…LC-MS/MS Analysis-To 10 L of human CSF sample, 10 L of an internal standard solution containing 13 C 15 N-amino acids was added, followed by the addition of 100 L of methyl alcohol. The mixture was vortexed for 10 seconds and centrifuged at 10.000 rpm for 10 minutes at 10°C.…”

Section: Biological Variation In An Experimentalmentioning

confidence: 99%

“…A systematic categorization of the CSF metabolome is necessary and expected to be beneficial for future biomarker discoveries. Recently, Wishart et al made a good start in exploring the human CSF metabolome with their computer-aided literature survey that resulted in 308 detectable metabolites in human CSF (13).…”

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confidence: 99%

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Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples

Stoop¹,

Coulier

Rosenling

et al. 2010

Molecular & Cellular Proteomics

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Section: Discussionsupporting

confidence: 87%

Section: Biological Variation In An Experimentalmentioning

confidence: 99%

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Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples

Stoop¹,

Coulier

Rosenling

et al. 2010

Molecular & Cellular Proteomics

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“…However, metabolome analysis of CSF remains to be an analytical challenge because of low concentrations of many metabolites present in CSF and the availability of only small volumes of samples. Through literature mining of more than 2000 books and journal articles, a total of 329 metabolites have been found to be detectable in various studies of human CSF (www.csfmetabolome.ca) [5]. Among them, only about 75 metabolites were reported to have concentrations of above 1 μM.…”

Section: Introductionmentioning

confidence: 99%

“…Analyzing metabolites in CSF is mostly done by using NMR [6][7][8][9][10], GC-MS [10,11], and LC-MS [10,[12][13][14]. In a report that compares different techniques for human CSF metabolome analysis [5], it was shown that the NMR technique could positively identify about 53 metabolites, GC-MS could identify 41 metabolites and LC-MS using Fourier-transfom ion cyclotron resonance (FTICR) MS could identify 17 metabolites. The combination of the three techniques identified a total of 70 different metabolites.…”

Section: Introductionmentioning

confidence: 99%

Qualitative Metabolome Analysis of Human Cerebrospinal Fluid by¹³C-/¹²C-Isotope Dansylation Labeling Combined with Liquid Chromatography Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

Guo

Bamforth

2011

J. Am. Soc. Mass Spectrom.

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Metabolome analysis of human cerebrospinal fluid (CSF) is challenging because of low abundance of metabolites present in a small volume of sample. We describe and apply a sensitive isotope labeling LC-MS technique for qualitative analysis of the CSF metabolome. After a CSF sample is divided into two aliquots, they are labeled by 13 C-dansyl and 12 C-dansyl chloride, respectively. The differentially labeled aliquots are then mixed and subjected to LC-MS using Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS). Dansylation offers significant improvement in the performance of chromatography separation and detection sensitivity. Moreover, peaks detected in the mass spectra can be readily analyzed for ion pair recognition and database search based on accurate mass and/or retention time information. It is shown that about 14,000 features can be detected in a 25-min LC-FTICR MS run of a dansyl-labeled CSF sample, from which about 500 metabolites can be profiled. Results from four CSF samples are compared to gauge the detectability of metabolites by this method. About 261 metabolites are commonly detected in replicate runs of four samples. In total, 1132 unique metabolite ion pairs are detected and 347 pairs (31%) matched with at least one metabolite in the Human Metabolome Database. We also report a dansylation library of 220 standard compounds and, using this library, about 85 metabolites can be positively identified. Among them, 21 metabolites have never been reported to be associated with CSF. These results illustrate that the dansylation LC-FTICR MS method can be used to analyze the CSF metabolome in a more comprehensive manner.

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NMR and Metabolomics

Chasapi

Karagkouni

Matzarapi

et al. 2019

Encyclopedia of Life Sciences

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Metabolomics is one of the most attractive whilst still developing field of omics sciences, studying metabolites and the alterations of their levels. As an approach, metabolomics has the potential to identify using high‐throughput analytical precision statistically significant alterations, covering a broad spectrum of metabolic processes. What metabolomics can offer are qualitative and quantitative information, incorporating the consideration of more variables in analytical procedures. Measuring of metabolites and metabolic profiling provide an instant ‘snapshot’ which permits the follow up of the dynamics of complex biological systems and their mechanisms under physiological or abnormal conditions. Nuclear magnetic resonance (NMR) provides an excellent technique for profiling the biological fluids and is especially adept at characterising complex solutions. Advances in biochemical data obtained from NMR spectra allow us to observe the metabolome in a very accurate manner and thus estimate the complex index of biochemical processes, determining the health status of an organism. To date, metabolomics profiling is a powerful approach for examining disease‐related metabolic changes and is highly effective in the identification of new biomarkers. Key Concepts NMR is a novel, noninvasive, fast, accurate and reproducible bioanalytical method for metabolites identification and quantification in biological samples. Simple 1 H 1D NMR spectra are exploited for the definition of the physiological healthy status of organism's metabolism, based on a specific spectral pattern. NMR experiments selection depends on the biological fluid of interest. Metabolites identification and quantification and their role in a metabolomic experiment. The advantages of metabolic profiling and its utility in a potential diagnostic model. Monitoring of an individual's metabolic responses through the examination of its spectral fingerprint along specific time points. Significant alterations in metabolites concentrations are meaningful to exact interactions of pathways, perturbations and metabolite–metabolite correlations. Computational tools and global repositories in service of metabolomic data. Multivariate analysis techniques and their implementation in the field of NMR metabolomics. NMR metabolomics in clinical research, the intervention of the field and the impact in accessing unknown biological phenomena.

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The human cerebrospinal fluid metabolome

Cited by 316 publications

References 31 publications

Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples

Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples

Qualitative Metabolome Analysis of Human Cerebrospinal Fluid by¹³C-/¹²C-Isotope Dansylation Labeling Combined with Liquid Chromatography Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

NMR and Metabolomics

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The human cerebrospinal fluid metabolome

Cited by 316 publications

References 31 publications

Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples

Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples

Qualitative Metabolome Analysis of Human Cerebrospinal Fluid by13C-/12C-Isotope Dansylation Labeling Combined with Liquid Chromatography Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

NMR and Metabolomics

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Qualitative Metabolome Analysis of Human Cerebrospinal Fluid by¹³C-/¹²C-Isotope Dansylation Labeling Combined with Liquid Chromatography Fourier Transform Ion Cyclotron Resonance Mass Spectrometry