| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Wuolikainen, Anna, et al.
(författare)
-
Predictive metabolomics for detection, interpretation and validation of metabolite patterns in human cerebrospinal fluid
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We here present our predictive metabolomics approach for screening and comparing metabolomics data from human cerebrospinal fluid (CSF) generated by gas chromatography-time of flight mass spectrometry (GC-TOFMS). The approach is based on a combination of hierarchical multivariate curve resolution (HMCR) and manual integration of the GC–TOFMS data for quantification and identification of metabolites in multiple CSF samples. Chemometric data analysis, orthogonal partial least squares (OPLS), for multiple CSF sample comparisons. We show how the predictive feature of both HMCR and OPLS can be used for biomarker detection and verification as well as for diagnostic modelling. To exemplify the capability of the method we have used human CSF from two test subjects aliquoted into 44 tubes stored at either -80 °C or -20 °C as a model system. A total of 170 potential metabolites were resolved from the GC-TOFMS data using HMCR. OPLS modelling revealed a clear separation of the samples according to storage temperature, with a prediction accuracy of 100% using a test set.
|
|
| 5. |
- Wuolikainen, Anna, et al.
(författare)
-
Studies of the human cerebrospinal fluid metabolome reveal alterations associated with amyotrophic lateral sclerosis and subtypes of the disease
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The composition of the metabolome in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis is unknown. Previous studies of single metabolites have shown conflicting results.Methods: Using GC-TOFMS and multivariate statistical modeling, we studied the metabolome signature of ~120 compounds in the cerebrospinal fluid of ALS patients stratified according to hereditary disposition and clinical subtypes of the disease.Findings: Sporadic ALS has a heterogeneous metabolite signature in the CSF, in some patients being almost identical to controls. Familial ALS without SOD1 gene mutation is less heterogeneous than sporadic ALS. The metabolome of the CSF of the 17 ALS patients with a SOD1 gene mutation appeared as a separate homogeneous group. Analysis of single metabolites revealed that glutamate, pyroglutamate and glutamine were all reduced, in particular in patients with a familial disposition.Interpretation: There are significant differences in the metabolite profile and composition among patients with familial ALS, sporadic ALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be different. Patients with a genetic predisposition to ALS have a more distinct signature than patients with a sporadic disease.
|
|
