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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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Related in: MedlinePlus

PLS results.Analysis of C18 data from ALS patients A/ spinal-onset (red) and bulbar-onset (turquoise); B/ female (red) and male (turquoise) - Each dot correspond to one patient (average of 9 spectra per patient).
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pone-0079733-g005: PLS results.Analysis of C18 data from ALS patients A/ spinal-onset (red) and bulbar-onset (turquoise); B/ female (red) and male (turquoise) - Each dot correspond to one patient (average of 9 spectra per patient).

Mentions: In this study, 32 ALS patients had a spinal onset (10 women / 22 men) and 8 a bulbar onset (4 women / 4 men). To determine if some peaks are significant signals to discriminate between ALS subtypes, an orientated statistical analysis of C18 MALDI data was done. PLS (Partial Least Square) analysis clearly shows that spinal and bulbar ALS patient can be differentiated on the base of the C18 MALDI data (Figure 5.A). In the same way, the PLS analysis based on the gender shows that C18 MALDI profiles can also allow the ALS patients classification depending on the gender (Figure 5.B). However, implicated signals (p-value<0.05) in gender differentiation do not match with the list of significant peaks that lead to the ALS subtype differentiation (Table 5). On the other hand, only one peak selected as gender discriminative signal appears in 5 of the 10 SVM-based models defined for ALS diagnostic during the discovery step (Table 2, peak 5004). However, as this peak was not present in all of the 10 SVM-based models for ALS diagnostic, it has not been selected for the final model.


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)

PLS results.Analysis of C18 data from ALS patients A/ spinal-onset (red) and bulbar-onset (turquoise); B/ female (red) and male (turquoise) - Each dot correspond to one patient (average of 9 spectra per patient).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0079733-g005: PLS results.Analysis of C18 data from ALS patients A/ spinal-onset (red) and bulbar-onset (turquoise); B/ female (red) and male (turquoise) - Each dot correspond to one patient (average of 9 spectra per patient).
Mentions: In this study, 32 ALS patients had a spinal onset (10 women / 22 men) and 8 a bulbar onset (4 women / 4 men). To determine if some peaks are significant signals to discriminate between ALS subtypes, an orientated statistical analysis of C18 MALDI data was done. PLS (Partial Least Square) analysis clearly shows that spinal and bulbar ALS patient can be differentiated on the base of the C18 MALDI data (Figure 5.A). In the same way, the PLS analysis based on the gender shows that C18 MALDI profiles can also allow the ALS patients classification depending on the gender (Figure 5.B). However, implicated signals (p-value<0.05) in gender differentiation do not match with the list of significant peaks that lead to the ALS subtype differentiation (Table 5). On the other hand, only one peak selected as gender discriminative signal appears in 5 of the 10 SVM-based models defined for ALS diagnostic during the discovery step (Table 2, peak 5004). However, as this peak was not present in all of the 10 SVM-based models for ALS diagnostic, it has not been selected for the final model.

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