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Plasma peptide biomarker discovery for amyotrophic lateral sclerosis by MALDI-TOF mass spectrometry profiling.

Conraux L, Pech C, Guerraoui H, Loyaux D, Ferrara P, Guillemot JC, Meininger V, Pradat PF, Salachas F, Bruneteau G, Le Forestier N, Lacomblez L - PLoS ONE (2013)

Bottom Line: In our study, we looked for peptide biomarkers in plasma samples using reverse phase magnetic beads (C18 and C8) and MALDI-TOF mass spectrometry analysis.These two SVM-based models end up in excellent separations between the 2 groups of patients (recognition capability overall classes > 97%) and classify blinded samples (10 ALS and 10 healthy age-matched controls) with very high sensitivities and specificities (>90%).Some of these discriminant peaks have been identified by Mass Spectrometry (MS) analyses and correspond to (or are fragments of) major plasma proteins, partly linked to the blood coagulation.

View Article: PubMed Central - PubMed

Affiliation: Exploratory Unit, Sanofi, Toulouse, France.

ABSTRACT
The diagnostic of Amyotrophic lateral sclerosis (ALS) remains based on clinical and neurophysiological observations. The actual delay between the onset of the symptoms and diagnosis is about 1 year, preventing early inclusion of patients into clinical trials and early care of the disease. Therefore, finding biomarkers with high sensitivity and specificity remains urgent. In our study, we looked for peptide biomarkers in plasma samples using reverse phase magnetic beads (C18 and C8) and MALDI-TOF mass spectrometry analysis. From a set of ALS patients (n=30) and healthy age-matched controls (n=30), C18- or C8-SVM-based models for ALS diagnostic were constructed on the base of the minimum of the most discriminant peaks. These two SVM-based models end up in excellent separations between the 2 groups of patients (recognition capability overall classes > 97%) and classify blinded samples (10 ALS and 10 healthy age-matched controls) with very high sensitivities and specificities (>90%). Some of these discriminant peaks have been identified by Mass Spectrometry (MS) analyses and correspond to (or are fragments of) major plasma proteins, partly linked to the blood coagulation.

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Principal component analysis.The first 3 principal components which account for most of the variance in the original data set are shown A) from MS-data of C8-beads sample preparation and B) from MS-data of C18-beads sample preparation; ALS patients (red) and healthy controls (green) ; 1 dot per patient (average of 9 spectra per patient); Eigenvalues screen plots are at the right of each PCA.
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pone-0079733-g002: Principal component analysis.The first 3 principal components which account for most of the variance in the original data set are shown A) from MS-data of C8-beads sample preparation and B) from MS-data of C18-beads sample preparation; ALS patients (red) and healthy controls (green) ; 1 dot per patient (average of 9 spectra per patient); Eigenvalues screen plots are at the right of each PCA.

Mentions: We analyzed the plasma peptide profiles of 40 ALS patients and 40 healthy volunteers. All 80 plasma samples were processed fully automatically as a single batch and with automated MALDI-TOF MS analysis. After normalization and alignment of the all processed spectra, 158 unique peaks, with a signal to noise threshold equal or greater than 3 on the average spectrum, could be detected in the C18 dataset and 131 unique peaks in the C8 dataset. MALDI profiles are displayed on Figure 1. Matrixes containing the normalized intensities of all detected peaks from peptide extracted on magnetic beads coated with C8 or C18 phase for each of the samples (9 spectra per patients) were then used for unsupervised statistical analyses using principal component analysis (PCA). Two separate point clouds corresponding each to one class of samples, ALS patients and healthy controls, are clearly highlighted by these analyses (Figure 2).


Plasma peptide biomarker discovery for amyotrophic lateral sclerosis by MALDI-TOF mass spectrometry profiling.

Conraux L, Pech C, Guerraoui H, Loyaux D, Ferrara P, Guillemot JC, Meininger V, Pradat PF, Salachas F, Bruneteau G, Le Forestier N, Lacomblez L - PLoS ONE (2013)

Principal component analysis.The first 3 principal components which account for most of the variance in the original data set are shown A) from MS-data of C8-beads sample preparation and B) from MS-data of C18-beads sample preparation; ALS patients (red) and healthy controls (green) ; 1 dot per patient (average of 9 spectra per patient); Eigenvalues screen plots are at the right of each PCA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818176&req=5

pone-0079733-g002: Principal component analysis.The first 3 principal components which account for most of the variance in the original data set are shown A) from MS-data of C8-beads sample preparation and B) from MS-data of C18-beads sample preparation; ALS patients (red) and healthy controls (green) ; 1 dot per patient (average of 9 spectra per patient); Eigenvalues screen plots are at the right of each PCA.
Mentions: We analyzed the plasma peptide profiles of 40 ALS patients and 40 healthy volunteers. All 80 plasma samples were processed fully automatically as a single batch and with automated MALDI-TOF MS analysis. After normalization and alignment of the all processed spectra, 158 unique peaks, with a signal to noise threshold equal or greater than 3 on the average spectrum, could be detected in the C18 dataset and 131 unique peaks in the C8 dataset. MALDI profiles are displayed on Figure 1. Matrixes containing the normalized intensities of all detected peaks from peptide extracted on magnetic beads coated with C8 or C18 phase for each of the samples (9 spectra per patients) were then used for unsupervised statistical analyses using principal component analysis (PCA). Two separate point clouds corresponding each to one class of samples, ALS patients and healthy controls, are clearly highlighted by these analyses (Figure 2).

Bottom Line: In our study, we looked for peptide biomarkers in plasma samples using reverse phase magnetic beads (C18 and C8) and MALDI-TOF mass spectrometry analysis.These two SVM-based models end up in excellent separations between the 2 groups of patients (recognition capability overall classes > 97%) and classify blinded samples (10 ALS and 10 healthy age-matched controls) with very high sensitivities and specificities (>90%).Some of these discriminant peaks have been identified by Mass Spectrometry (MS) analyses and correspond to (or are fragments of) major plasma proteins, partly linked to the blood coagulation.

View Article: PubMed Central - PubMed

Affiliation: Exploratory Unit, Sanofi, Toulouse, France.

ABSTRACT
The diagnostic of Amyotrophic lateral sclerosis (ALS) remains based on clinical and neurophysiological observations. The actual delay between the onset of the symptoms and diagnosis is about 1 year, preventing early inclusion of patients into clinical trials and early care of the disease. Therefore, finding biomarkers with high sensitivity and specificity remains urgent. In our study, we looked for peptide biomarkers in plasma samples using reverse phase magnetic beads (C18 and C8) and MALDI-TOF mass spectrometry analysis. From a set of ALS patients (n=30) and healthy age-matched controls (n=30), C18- or C8-SVM-based models for ALS diagnostic were constructed on the base of the minimum of the most discriminant peaks. These two SVM-based models end up in excellent separations between the 2 groups of patients (recognition capability overall classes > 97%) and classify blinded samples (10 ALS and 10 healthy age-matched controls) with very high sensitivities and specificities (>90%). Some of these discriminant peaks have been identified by Mass Spectrometry (MS) analyses and correspond to (or are fragments of) major plasma proteins, partly linked to the blood coagulation.

Show MeSH
Related in: MedlinePlus