Papers by Helmut E. Meyer
Proceedings of the National Academy of Sciences of the United States of America, Dec 1, 1988
PROTEOMICS, 2007
Proteomics Data Collection (ProDaC) is an EU funded &... more Proteomics Data Collection (ProDaC) is an EU funded "Coordination Action" within the 6(th) framework programme. It aims to simplify the publication, dissemination and utilization of proteomics data by establishing standards that will support broad data collection from the research community. The 1(st) ProDaC workshop 2007 (succeeding the kick-off meeting last year at the HUPO World Congress 2006) took place at the Ecole Normale Supérieur in Lyon, France. These workshops take place as regular meetings on a half-year basis. On Thursday April 26(th) 2007 the progress of the first six months of the project was presented by the leaders of each of the seven work packages.
PROTEOMICS, 2010
The organization and storage of proteomics data are challenging issues today and even more for th... more The organization and storage of proteomics data are challenging issues today and even more for the rising amount of information in the future. This review article describes the advantages of using Laboratory Information Management Systems (LIMS) in proteomics laboratories. Seven typical LIMS are explored in detail to describe their role in an even bigger interrelation. They are a central part of the proteomics data workflow, starting with data generation and ending with the publication in journals and repositories. Therefore, they enable community‐wide data utilization and further Systems Biology discoveries.
Analytical and Bioanalytical Chemistry, 2008
Microcharacterrization of Proteins
BIOspektrum, 2017
Extracellular vesicles (EV) are secreted by most cells and are present in every body fluid. They ... more Extracellular vesicles (EV) are secreted by most cells and are present in every body fluid. They can be seen as major players in the regulation and communication of cells. They are adressed as therapeutic and diagnostic tool for many disorders including neurodegenerative diseases. Distinct subpopulations of platelet derived EVs have been shown to contain high concentrations of Alzheimer's disease(AD)-associated proteins e. g. APP, APOE, lipids and miRNAs and thus might contribute actively to the progression of the disease.
Localization of phosphorylated amino acids within the primary structure of phosphorylated protein... more Localization of phosphorylated amino acids within the primary structure of phosphorylated proteins is a prerequisite for understanding their function. Of particular interest are those residues which are phosphorylated in vivo (endogenous phosphate), since these phospho-amino acids are physiologically relevant e.g. in the regulation of enzyme activities, ion channel mechanisms and other regulatory mechanisms.
Molecular & Cellular Proteomics, 2008
... REFERENCES. ↵ Wilkins, MR, Appel, RD, Van Eyk, JE, Chung, MC, Görg, A., Hecker, M., Huber, LA... more ... REFERENCES. ↵ Wilkins, MR, Appel, RD, Van Eyk, JE, Chung, MC, Görg, A., Hecker, M., Huber, LA, Langen, H., Link, AJ, Paik, YK, Patterson, SD, Pennington, SR, Rabilloud, T., Simpson, RJ, Weiss, W., Dunn MJ (2006 ) Guidelines for the next 10 years of proteomics. ...
Journal of Translational Medicine, 2016
Background: The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular mat... more Background: The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). Methods: MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed. Results: MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2•10 −16). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches). Conclusions: We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals.
BIOspektrum, 2012
The immune system has a keyrole in the protection against exogenous invaders like bacteria and vi... more The immune system has a keyrole in the protection against exogenous invaders like bacteria and viruses. Antibodies are key players in this battle. This protective role may change, if antibodies recognize self antigens as potential enemies. So called autoantibodies may have a deleterious function like, for example, in rheumatic disease. The role of antibodies in neurodegenerative disorders is unclear. Due to their lifelong memory function antibodies can be used as disease markers, like in rheumatic disease, but although to identify an infectious state.
PROTEOMICS, 2013
Contemporary protein microarrays such as the ProtoArray R are used for autoimmune antibody screen... more Contemporary protein microarrays such as the ProtoArray R are used for autoimmune antibody screening studies to discover biomarker panels. For ProtoArray data analysis, the software Prospector and a default workflow are suggested by the manufacturer. While analyzing a large data set of a discovery study for diagnostic biomarkers of the Parkinson's disease (ParkCHIP), we have revealed the need for distinct improvements of the suggested workflow concerning raw data acquisition, normalization and preselection method availability, batch effects, feature selection, and feature validation. In this work, appropriate improvements of the default workflow are proposed. It is shown that completely automatic data acquisition as a batch, a reimplementation of Prospector's pre-selection method, multivariate or hybrid feature selection, and validation of the selected protein panel using an independent test set define in combination an improved workflow for large studies.
PROTEOMICS, 2008
We have correlated transcriptomics, proteomics and toponomics analyses of hippocampus tissue of i... more We have correlated transcriptomics, proteomics and toponomics analyses of hippocampus tissue of inbred C57BL/6 mice to analyse the interrelationship of expressed genes and proteins at different levels of organization. We find that transcriptome and proteome levels of function as well as the topological organization of synaptic protein clusters, detected by toponomics at physiological sites of hippocampus CA3 region, are all largely conserved between different mice. While the number of different synaptic states, characterized by distinct synaptic protein clusters, is enormous (>155 000), these states together form synaptic networks defining distinct and mutually exclusive territories in the hippocampus tissue. The findings provide insight in the systems biology of gene expression on transcriptome, proteome and toponome levels of function in the same brain subregion. The approach will lay the ground for designing studies of neurodegeneration in mouse models and human brains.
Proceedings of the National Academy of Sciences, 1977
The three-dimensional structures of dogfish M4 (muscle) and pig H4 (heart) lactate dehydrogenase ... more The three-dimensional structures of dogfish M4 (muscle) and pig H4 (heart) lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) have been determined and correlated with the amino acid sequences of the dogfish M4, pig M4, pig H4, chicken M4, and chicken H4 lactate dehydrogenase isozymes. These results have been related to the known differences of physicochemical properties between the M and H lactate dehydrogenase isozymes. By far the largest structural alterations occur in the transition between the "apo" and "ternary complex" conformational states of the enzyme rather than between species or isozymes. The major catalytic difference can be explained by a replacement of alanine (in the M chain) with a glutamine (in the H chain) in the vicinity of the binding site of the coenzyme phosphates. The known immunological differentiation of the M and H isozymes is consistent with the differences in their amino acid sequences.
PLoS ONE, 2013
Detection of yet unknown subgroups showing differential gene or protein expression is a frequent ... more Detection of yet unknown subgroups showing differential gene or protein expression is a frequent goal in the analysis of modern molecular data. Applications range from cancer biology over developmental biology to toxicology. Often a control and an experimental group are compared, and subgroups can be characterized by differential expression for only a subgroup-specific set of genes or proteins. Finding such genes and corresponding patient subgroups can help in understanding pathological pathways, diagnosis and defining drug targets. The size of the subgroup and the type of differential expression determine the optimal strategy for subgroup identification. To date, commonly used software packages hardly provide statistical tests and methods for the detection of such subgroups. Different univariate methods for subgroup detection are characterized and compared, both on simulated and on real data. We present an advanced design for simulation studies: Data is simulated under different distributional assumptions for the expression of the subgroup, and performance results are compared against theoretical upper bounds. For each distribution, different degrees of deviation from the majority of observations are considered for the subgroup. We evaluate classical approaches as well as various new suggestions in the context of omics data, including outlier sum, PADGE, and kurtosis. We also propose the new FisherSum score. ROC curve analysis and AUC values are used to quantify the ability of the methods to distinguish between genes or proteins with and without certain subgroup patterns. In general, FisherSum for small subgroups and t-test for large subgroups achieve best results. We apply each method to a case-control study on Parkinson's disease and underline the biological benefit of the new method.
PLoS ONE, 2013
Background: Olfactory impairment is increasingly recognized as an early symptom in the developmen... more Background: Olfactory impairment is increasingly recognized as an early symptom in the development of Parkinson's disease. Testing olfactory function is a non-invasive method but can be time-consuming which restricts its application in clinical settings and epidemiological studies. Here, we investigate odor identification as a supportive diagnostic tool for Parkinson's disease and estimate the performance of odor subsets to allow a more rapid testing of olfactory impairment. Methodology/Principal Findings: Odor identification was assessed with 16 Sniffin' sticks in 148 Parkinson patients and 148 healthy controls. Risks of olfactory impairment were estimated with proportional odds models. Random forests were applied to classify Parkinson and non-Parkinson patients. Parkinson patients were rarely normosmic (identification of more than 12 odors; 16.8%) and identified on average seven odors whereas the reference group identified 12 odors and showed a higher prevalence of normosmy (31.1%). Parkinson patients with rigidity dominance had a twofold greater prevalence of olfactory impairment. Disease severity was associated with impairment of odor identification (per score point of the Hoehn and Yahr rating OR 1.87, 95% CI 1.26-2.77). Age-related impairment of olfaction showed a steeper gradient in Parkinson patients. Coffee, peppermint, and anise showed the largest difference in odor identification between Parkinson patients and controls. Random forests estimated a misclassification rate of 22.4% when comparing Parkinson patients with healthy controls using all 16 odors. A similar rate (23.8%) was observed when only the three aforementioned odors were applied. Conclusions/Significance: Our findings indicate that testing odor identification can be a supportive diagnostic tool for Parkinson's disease. The application of only three odors performed well in discriminating Parkinson patients from controls, which can facilitate a wider application of this method as a point-of-care test.
Journal of Proteome Research, 2007
Understanding the function of membrane proteins is of fundamental importance due to their crucial... more Understanding the function of membrane proteins is of fundamental importance due to their crucial roles in many cellular processes and their direct association with human disorders. However, their analysis poses a special challenge, largely due to their highly amphipathic nature. Until recently, analyses of proteomic samples mainly were performed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), due to the unprecedented separation power of the technique. However, in conventional 2D-PAGE membrane proteins are generally underrepresented due to their tendency to precipitate during isoelectric focusing and their inefficient transfer from the first to the second dimension. As a consequence, several other separation techniques, primarily based on liquid chromatography (LC), have been employed for analysis of this group of proteins. In the present study, different LC-based methods were compared for the analysis of crude protein extracts. One-and two-dimensional highperformance liquid chromatographic (1D-and 2D-HPLC) separations of brain protein tryptic digests with a predicted concentration range of up to 5 orders of magnitude were found to be insufficient, thus making a preceding fractionation step necessary. An additional protein separation step was introduced and a 3D-PAGE-HPLC analysis was performed. The results of these experiments are compared with results of 2D-PAGE/matrix-assisted laser desorption ionization mass spectrometric (MALDI MS) analyses of the same samples. Features, challenges, advantages, and disadvantages of the respective systems are discussed. The brain (mouse and human) was chosen as the analyzed tissue as it is of high interest in medical and pharmaceutical research into neurological diseases such as multiple sclerosis, stroke, Alzheimer's disease, and Parkinson's disease. The study is part of our ongoing research aimed at identifying new biomarkers for neurodegenerative diseases.
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Papers by Helmut E. Meyer