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Peptidome analysis of cerebrospinal fluid by LC-MALDI MS.

Hölttä M, Zetterberg H, Mirgorodskaya E, Mattsson N, Blennow K, Gobom J - PLoS ONE (2012)

Bottom Line: Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features.Out of these, 730 peptides were identified by MS/MS.The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system.

View Article: PubMed Central - PubMed

Affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by mass spectrometry. A method was developed for preparation of peptide extracts from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features. Out of these, 730 peptides were identified by MS/MS. The majority of these peptides have not been previously reported in CSF. The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system. These results support the notion that CSF peptidomics may be viable complement to proteomics in the search of biomarkers of CNS disorders.

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Related in: MedlinePlus

Stacked histogram of all peptide matches as a function of ion score.Peptide matches were retrieved that fulfilled the criteria: ion score >15 and at least one peptide match with ion score >27 per protein. The coloured segments indicate the number of validated (green) and rejected (red) peptide matches.
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pone-0042555-g003: Stacked histogram of all peptide matches as a function of ion score.Peptide matches were retrieved that fulfilled the criteria: ion score >15 and at least one peptide match with ion score >27 per protein. The coloured segments indicate the number of validated (green) and rejected (red) peptide matches.

Mentions: A histogram of the number of manually validated and rejected peptide matches as a function of ion score (Figure 3) shows that quite a large number of peptide hits with low ion score could be validated. A total of 730 peptide matches were validated. The 22% increase of assigned peptides by manual evaluation compared to the 596 peptides identified with an FDR of 1% in the Mascot database search is significant and suggests that, particularly for the analysis of singly-charged ions, search algorithms may be improved by implementing amino acid- and charge-based fragmentation schemes in their scoring algorithms.


Peptidome analysis of cerebrospinal fluid by LC-MALDI MS.

Hölttä M, Zetterberg H, Mirgorodskaya E, Mattsson N, Blennow K, Gobom J - PLoS ONE (2012)

Stacked histogram of all peptide matches as a function of ion score.Peptide matches were retrieved that fulfilled the criteria: ion score >15 and at least one peptide match with ion score >27 per protein. The coloured segments indicate the number of validated (green) and rejected (red) peptide matches.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412831&req=5

pone-0042555-g003: Stacked histogram of all peptide matches as a function of ion score.Peptide matches were retrieved that fulfilled the criteria: ion score >15 and at least one peptide match with ion score >27 per protein. The coloured segments indicate the number of validated (green) and rejected (red) peptide matches.
Mentions: A histogram of the number of manually validated and rejected peptide matches as a function of ion score (Figure 3) shows that quite a large number of peptide hits with low ion score could be validated. A total of 730 peptide matches were validated. The 22% increase of assigned peptides by manual evaluation compared to the 596 peptides identified with an FDR of 1% in the Mascot database search is significant and suggests that, particularly for the analysis of singly-charged ions, search algorithms may be improved by implementing amino acid- and charge-based fragmentation schemes in their scoring algorithms.

Bottom Line: Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features.Out of these, 730 peptides were identified by MS/MS.The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system.

View Article: PubMed Central - PubMed

Affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by mass spectrometry. A method was developed for preparation of peptide extracts from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features. Out of these, 730 peptides were identified by MS/MS. The majority of these peptides have not been previously reported in CSF. The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system. These results support the notion that CSF peptidomics may be viable complement to proteomics in the search of biomarkers of CNS disorders.

Show MeSH
Related in: MedlinePlus