MOTIVATION: The discovery of new and unexpected biomarkers in cardiovascular disease is a highly data-driven process that requires the complementary power of modern metabolite profiling technologies, bioinformatics and biostatistics. Clinical biomarkers of early myocardial injury are lacking. A prospective biomarker cohort study was carried out to identify, categorize and profile kinetic patterns of early metabolic biomarkers of planned myocardial infarction (PMI) and spontaneous (SMI) myocardial infarction. We applied a targeted mass spectrometry (MS)-based metabolite profiling platform to serial blood samples drawn from carefully phenotyped patients undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy serving as a human model of PMI. Patients with SMI and patients undergoing catheterization without induction of myocardial infarction served as positive and negative controls to assess generalizability of markers identified in PMI. RESULTS: To identify metabolites of high predictive value in tandem mass spectrometry data, we introduced a new feature selection method for the categorization of metabolic signatures into three classes of weak, moderate and strong predictors, which can be easily applied to both paired and unpaired samples. Our paradigm outperformed standard null-hypothesis significance testing and other popular methods for feature selection in terms of the area under the receiver operating curve and the product of sensitivity and specificity. Our results emphasize that this new method was able to identify, classify and validate alterations of levels in multiple metabolites participating in pathways associated with myocardial injury as early as 10 min after PMI. AVAILABILITY: The algorithm as well as supplementary material is available for download at: www.umit.at/page.cfm?vpath=departments/technik/iebe/tools/bi

MOTIVATION: Alcoholic fatty liver disease (AFLD) and non-AFLD (NAFLD) can progress to severe liver diseases such as steatohepatitis, cirrhosis and cancer. Thus, the detection of early liver disease is essential; however, minimal invasive diagnostic methods in clinical hepatology still lack specificity. RESULTS: Ion molecule reaction mass spectrometry (IMR-MS) was applied to a total of 126 human breath gas samples comprising 91 cases (AFLD, NAFLD and cirrhosis) and 35 healthy controls. A new feature selection modality termed Stacked Feature Ranking (SFR) was developed to identify potential liver disease marker candidates in breath gas samples, relying on the combination of different entropy- and correlation-based feature ranking methods including statistical hypothesis testing using a two-level architecture with a suggestion and a decision layer. We benchmarked SFR against four single feature selection methods, a wrapper and a recently described ensemble method, indicating a significantly higher discriminatory ability of up to 10-15% for the SFR selected gas compounds expressed by the area under the ROC curve (AUC) of 0.85-0.95. Using this approach, we were able to identify unexpected breath gas marker candidates in liver disease of high predictive value. A literature study further supports top-ranked markers to be associated with liver disease. We propose SFR as a powerful tool for biomarker search in breath gas and other biological samples using mass spectrometry. AVAILABILITY: The algorithm SFR and IMR-MS datasets are available under http://biomed.umit.at/page.cfm?pageid=526.

MOTIVATION: Prostate cancer is the most prevalent tumor in males and its incidence is expected to increase as the population ages. Prostate cancer is treatable by excision if detected at an early enough stage. The challenges of early diagnosis require the discovery of novel biomarkers and tools for prostate cancer management. RESULTS: We developed a novel feature selection algorithm termed as associative voting (AV) for identifying biomarker candidates in prostate cancer data measured via targeted metabolite profiling MS/MS analysis. We benchmarked our algorithm against two standard entropy-based and correlation-based feature selection methods [Information Gain (IG) and ReliefF (RF)] and observed that, on a variety of classification tasks in prostate cancer diagnosis, our algorithm identified subsets of biomarker candidates that are both smaller and show higher discriminatory power than the subsets identified by IG and RF. A literature study confirms that the highest ranked biomarker candidates identified by AV have independently been identified as important factors in prostate cancer development. AVAILABILITY: The algorithm can be downloaded from the following http://biomed.umit.at/page.cfm?pageid=516.