Analysis of proteins from cerebrospinal fluid tests in search of biomarkers characterizing Multiple sclerosis

There are contradicting theories describing Multiple sclerosis (MS). This study attempts to understand MS through interpreting the bio-markers of MS. Recursive feature elimination with cross validation (RFECV) was used to select bio-markers (proteins) for MS and to detect inflammation in patients. Principal components plots of proteins selected to distinguish between patients with MS and patients without MS were not only successful in separating patients with MS and patients without MS, but also showed two types of MS patients. The first type was MS patients with inflammation and the second type was MS patients without inflammation. This finding proposes inflammation to be a secondary effect of MS instead of a primary effect. The proteins in the principal component plots were related to inflammation and neuron development/regeneration. The types of proteins found together with the separate groupings of MS patients strengthen the hypothesis describing MS as a consequence of a defect in neuron regeneration where inflammation can sometimes but not always occur. This differs from the ’outside in model’ that is often referred to when explaining MS which depicts the autoimmune response as the primary cause of neuro-degeneration. Finally, Logistic regression and support vector classifiers were trained to classify patients with MS and patients with inflammation. Models distinguishing MS had a score of 90 percent on the test data, while models classifying inflammation had a score of 98 percent on the test data.M-D

Analysis of proteins from cerebrospinal fluid tests in search of biomarkers characterizing Multiple sclerosis

There are contradicting theories describing Multiple sclerosis (MS). This study attempts to understand MS through interpreting the bio-markers of MS. Recursive feature elimination with cross validation (RFECV) was used to select bio-markers (proteins) for MS and to detect inflammation in patients. Principal components plots of proteins selected to distinguish between patients with MS and patients without MS were not only successful in separating patients with MS and patients without MS, but also showed two types of MS patients. The first type was MS patients with inflammation and the second type was MS patients without inflammation. This finding proposes inflammation to be a secondary effect of MS instead of a primary effect. The proteins in the principal component plots were related to inflammation and neuron development/regeneration. The types of proteins found together with the separate groupings of MS patients strengthen the hypothesis describing MS as a consequence of a defect in neuron regeneration where inflammation can sometimes but not always occur. This differs from the ’outside in model’ that is often referred to when explaining MS which depicts the autoimmune response as the primary cause of neuro-degeneration. Finally, Logistic regression and support vector classifiers were trained to classify patients with MS and patients with inflammation. Models distinguishing MS had a score of 90 percent on the test data, while models classifying inflammation had a score of 98 percent on the test data

Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis

Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease

Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis

Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease

Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis

Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease