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  • Publication
    Comparison of different statistical approaches for urinary peptide biomarker detection in the context of coronary artery disease
    Background: When combined with a clinical outcome variable, the size, complexity and nature of mass-spectrometry proteomics data impose great statistical challenges in the discovery of potential disease-associated biomarkers. The purpose of this study was thus to evaluate the effectiveness of different statistical methods applied for urinary proteomic biomarker discovery and different methods of classifier modelling in respect of the diagnosis of coronary artery disease in 197 study subjects and the prognostication of acute coronary syndromes in 368 study subjects. Results: Computing the discovery sub-cohorts comprising 2=3 of the study subjects based on the Wilcoxon rank sum test, t-score, cat-score, binary discriminant analysis and random forests provided largely different numbers (ranging from 2 to 398) of potential peptide biomarkers. Moreover, these biomarker patterns showed very little overlap limited to fragments of type I and III collagens as the common denominator. However, these differences in biomarker patterns did mostly not translate into significant differently performing diagnostic or prognostic classifiers modelled by support vector machine, diagonal discriminant analysis, linear discriminant analysis, binary discriminant analysis and random forest. This was even true when different biomarker patterns were combined into master-patterns. Conclusion: In conclusion, our study revealed a very considerable dependence of peptide biomarker discovery on statistical computing of urinary peptide profiles while the observed diagnostic and/or prognostic reliability of classifiers was widely independent of the modelling approach. This may however be due to the limited statistical power in classifier testing. Nonetheless, our study showed that urinary proteome analysis has the potential to provide valuable biomarkers for coronary artery disease mirroring especially alterations in the extracellular matrix. It further showed that for a comprehensive discovery of biomarkers and thus of pathological information, the results of different statistical methods may best be combined into a master pattern that then can be used for classifier modelling.
      283ScopusĀ© Citations 6
  • Publication
    A Bayesian algorithm for detecting differentially expressed proteins and its application in breast cancer research
    (Springer Nature, 2016-07-22) ;
    Presence of considerable noise and missing data points make analysis of mass-spectrometry (MS) based proteomic data a challenging task. The missing values in MS data are caused by the inability of MS machines to reliably detect proteins whose abundances fall below the detection limit. We developed a Bayesian algorithm that exploits this knowledge and uses missing data points as a complementary source of information to the observed protein intensities in order to find differentially expressed proteins by analysing MS based proteomic data. We compared its accuracy with many other methods using several simulated datasets. It consistently outperformed other methods. We then used it to analyse proteomic screens of a breast cancer (BC) patient cohort. It revealed large differences between the proteomic landscapes of triple negative and Luminal A, which are the most and least aggressive types of BC. Unexpectedly, majority of these differences could be attributed to the direct transcriptional activity of only seven transcription factors some of which are known to be inactive in triple negative BC. We also identified two new proteins which significantly correlated with the survival of BC patients, and therefore may have potential diagnostic/prognostic values.
      240ScopusĀ© Citations 5