A combined dataset of human cerebrospinal fluid proteins identified by multi‐dimensional chromatography and tandem mass spectrometry

Pan, Sheng; Zhu, David C.; Quinn, Joseph F.; Peskind, Elaine R.; Montine, Thomas J.; Lin, Biaoyang; Taylor, Greg; Eng, Jimmy K.; Zhang, Jing

doi:10.1002/pmic.200600756

Cited by 107 publications

(95 citation statements)

References 34 publications

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“…Concordance in protein ratios and overall trends is greatest between the two laboratories identifying the highest number of proteins. This supports an argument that future studies with resource limitations should emphasize the depth of protein coverage and include multiple laboratories only if their experimental methods complement each other in terms of the protein observations (30). Our study also suggests that data integration plays a central role in studies to identify biomarkers as statistical significance could not have been demonstrated without the ability to evaluate changes in predefined groups of proteins using the gene set enrichment analysis (GSEA) approach.…”

supporting

confidence: 75%

“…In practice, one can use these values as filters to generate lists by lab for protein groups that significantly change with disease status. Because of limitations in the accuracy and comprehensiveness of any one data set due to the complex nature of the samples (19,30) and current technology (42), a combination of these results across labs using completely different experimental designs and proteomics platforms will improve the accuracy, consistency, and comprehensiveness of protein candidate lists. Here we used a method described under "Experimental Procedures" of first performing a comprehensive search on all applicable data and then synthesizing the quantitation results.…”

Section: Resultsmentioning

confidence: 99%

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Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease

Fang¹,

Strand

Law³

et al. 2009

Molecular & Cellular Proteomics

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We integrated five sets of proteomics data profiling the constituents of cerebrospinal fluid (CSF) derived from Huntington disease (HD)-affected and -unaffected individuals with genomics data profiling various human and mouse tissues, including the human HD brain. Based on an integrated analysis, we found that brain-specific proteins are 1.8 times more likely to be observed in CSF than in plasma, that brain-specific proteins tend to decrease in HD CSF compared with unaffected CSF, and that 81% of brainspecific proteins have quantitative changes concordant with transcriptional changes identified in different regions of HD brain. The proteins found to increase in HD CSF tend to be liver-associated. These protein changes are consistent with neurodegeneration, microgliosis, and astrocytosis known to occur in HD. We also discuss concordance between laboratories and find that ratios of individual proteins can vary greatly, but the overall trends with respect to brain or liver specificity were consistent. Concordance is highest between the two laboratories observing the largest numbers of proteins. Huntington disease (HD)1 is an inherited neurodegenerative disorder characterized by progressive cognitive decline and psychiatric and movement symptoms. The cause of the disease is the expansion of trinucleotide (CAG) repeats in the coding region of the htt gene that translates into a polyglutamine tract in the huntingtin protein (1). Currently no treatment has been shown to delay the onset of the disease or slow its progression in patients. To speed assessment of therapies in clinical trials, it is critical to identify biological markers that can accurately monitor disease progression.Several genomics and proteomics approaches to identifying biomarkers for HD have been undertaken previously. Genomics studies have determined the molecular phenotype of human HD brain (2) and different tissues of HD mouse models at the mRNA level (3-6). Proteomics approaches have been applied to brain tissues of HD mouse models and humans to identify candidate markers (7-9). Blood plasma in particular has received considerable attention recently because of its ready accessibility clinically (10, 11). The candidate protein biomarkers identified in the blood proteomics studies are largely known inflammatory markers. Because HD is regarded primarily as a neurodegenerative disease, it is not entirely clear how directly general markers of neuroinflammation relate to the pathophysiology of HD, although astrocytosis and microgliosis (12) are prominent components of HD in its mid-to late stages (13). Another concern regarding markers discovered primarily in blood is that the blood-brain barrier may restrict brain proteins from entering plasma, and so plasma candidates may not directly reflect HD progression in the brain.Cerebrospinal fluid (CSF) is a more relevant biomaterial for biomarker discovery because it is proximal to the brain; it occupies the subarachnoid space of the central nervous system and the ventricular system around and inside the b...

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supporting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease

Fang¹,

Strand

Law³

et al. 2009

Molecular & Cellular Proteomics

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“…Recently, studies have been published with numerous identities and quantities of CSF proteins. Pan and co-workers were able to identify 2,594 proteins in well-characterized pooled human CSF samples using strict proteomics criteria with a combination of linear trap quadrupole LTQ-FT (Thermo Fisher Scientific, Bremen, Germany) and MALDI TOF/TOF equipment (14). They were also able to quantify several proteins using a targeted LC MALDI TOF/TOF approach (15).…”

mentioning

confidence: 99%

Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples

Stoop¹,

Coulier

Rosenling

et al. 2010

Molecular & Cellular Proteomics

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“…Finally, an exhaustive view of CSF proteome was obtained by Fourier transform ICR which could identify more than 4000 different proteins [23,24].…”

Section: Proteomics Analysis Of the Normal Csf Proteomementioning

confidence: 99%

Clinical proteomics of the cerebrospinal fluid: Towards the discovery of new biomarkers

Roche

Gabelle

Lehmann

2008

Proteomics Clinical Apps

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The cerebrospinal fluid (CSF) circulates within the CNS where it plays an essential physiological role in homeostasis of neuronal cells. This biological fluid has an important protein diversity that results from both filtration of serum through the blood-brain barrier and production/secretion of neuronal peptides and proteins. Changes in CSF composition depend on blood proteome, CSF circulation alterations, as well as physiological or pathological brain status. Hence, CSF proteomic analysis gives a unique opportunity to detect and describe biomarkers in neurological affections. Although lumbar puncture is considered as invasive, post lumbar puncture events remain rare and minor. Nevertheless, CSF biological analysis is currently limited to a small number of parameters and clinical situations suggesting mainly meningitis, malignancies or dementia. Few CSF proteomic studies have been performed in comparison to those on blood. In this review, we will provide a proteomics description of the CSF, summarize the current clinical use of this fluid and describe its clinical proteomics examination.

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A combined dataset of human cerebrospinal fluid proteins identified by multi‐dimensional chromatography and tandem mass spectrometry

Cited by 107 publications

References 34 publications

Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease

Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease

Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples

Clinical proteomics of the cerebrospinal fluid: Towards the discovery of new biomarkers

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