Application of an efficient Bayesian discretization method to biomedical data

Background\ud Several data mining methods require data that are discrete, and other methods often perform better with discrete data. We introduce an efficient Bayesian discretization (EBD) method for optimal discretization of variables that runs efficiently on high-dimensional biomedical datasets. The EBD method consists of two components, namely, a Bayesian score to evaluate discretizations and a dynamic programming search procedure to efficiently search the space of possible discretizations. We compared the performance of EBD to Fayyad and Irani's (FI) discretization method, which is commonly used for discretization.\ud \ud Results\ud On 24 biomedical datasets obtained from high-throughput transcriptomic and proteomic studies, the classification performances of the C4.5 classifier and the naïve Bayes classifier were statistically significantly better when the predictor variables were discretized using EBD over FI. EBD was statistically significantly more stable to the variability of the datasets than FI. However, EBD was less robust, though not statistically significantly so, than FI and produced slightly more complex discretizations than FI.\ud \ud Conclusions\ud On a range of biomedical datasets, a Bayesian discretization method (EBD) yielded better classification performance and stability but was less robust than the widely used FI discretization method. The EBD discretization method is easy to implement, permits the incorporation of prior knowledge and belief, and is sufficiently fast for application to high-dimensional data

Knowledge-based variable selection for learning rules from proteomic data

<p>Abstract</p> <p>Background</p> <p>The incorporation of biological knowledge can enhance the analysis of biomedical data. We present a novel method that uses a proteomic knowledge base to enhance the performance of a rule-learning algorithm in identifying putative biomarkers of disease from high-dimensional proteomic mass spectral data. In particular, we use the Empirical Proteomics Ontology Knowledge Base (EPO-KB) that contains previously identified and validated proteomic biomarkers to select <it>m/z</it>s in a proteomic dataset prior to analysis to increase performance.</p> <p>Results</p> <p>We show that using EPO-KB as a pre-processing method, specifically selecting all biomarkers found only in the biofluid of the proteomic dataset, reduces the dimensionality by 95% and provides a statistically significantly greater increase in performance over no variable selection and random variable selection.</p> <p>Conclusion</p> <p>Knowledge-based variable selection even with a sparsely-populated resource such as the EPO-KB increases overall performance of rule-learning for disease classification from high-dimensional proteomic mass spectra.</p

A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface

Aberrant interactions between the host and the intestinal bacteria are thought to contribute to the pathogenesis of many digestive diseases. However, studying the complex ecosystem at the human mucosal-luminal interface (MLI) is challenging and requires an integrative systems biology approach. Therefore, we developed a novel method integrating lavage sampling of the human mucosal surface, high-throughput proteomics, and a unique suite of bioinformatic and statistical analyses. Shotgun proteomic analysis of secreted proteins recovered from the MLI confirmed the presence of both human and bacterial components. To profile the MLI metaproteome, we collected 205 mucosal lavage samples from 38 healthy subjects, and subjected them to high-throughput proteomics. The spectral data were subjected to a rigorous data processing pipeline to optimize suitability for quantitation and analysis, and then were evaluated using a set of biostatistical tools. Compared to the mucosal transcriptome, the MLI metaproteome was enriched for extracellular proteins involved in response to stimulus and immune system processes. Analysis of the metaproteome revealed significant individual-related as well as anatomic region-related (biogeographic) features. Quantitative shotgun proteomics established the identity and confirmed the biogeographic association of 49 proteins (including 3 functional protein networks) demarcating the proximal and distal colon. This robust and integrated proteomic approach is thus effective for identifying functional features of the human mucosal ecosystem, and a fresh understanding of the basic biology and disease processes at the MLI. © 2011 Li et al

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Knowledge-based variable selection for learning rules from proteomic data

Background: The incorporation of biological knowledge can enhance the analysis of biomedical data. We present a novel method that uses a proteomic knowledge base to enhance the performance of a rule-learning algorithm in identifying putative biomarkers of disease from high-dimensional proteomic mass spectral data. In particular, we use the Empirical Proteomics Ontology Knowledge Base (EPO-KB) that contains previously identified and validated proteomic biomarkers to select m/zs in a proteomic dataset prior to analysis to increase performance. Results: We show that using EPO-KB as a pre-processing method, specifically selecting all biomarkers found only in the biofluid of the proteomic dataset, reduces the dimensionality by 95% and provides a statistically significantly greater increase in performance over no variable selection and random variable selection. Conclusion: Knowledge-based variable selection even with a sparsely-populated resource such as the EPO-KB increases overall performance of rule-learning for disease classification from high-dimensional proteomic mass spectra. © 2009 Lustgarten et al; licensee BioMed Central Ltd