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Identification of a Common Gene Expression Signature in Dilated Cardiomyopathy Across Independent Microarray Studies

Andreas S. Barth, MD^_*,_*, Ruprecht Kuner, PhD, Andreas Buness, MSc, Markus Ruschhaupt, MSc^,, Sylvia Merk, DVM^,||, Ludwig Zwermann, MD^_*, Stefan Kääb, MD^_*, Eckart Kreuzer, MD, Gerhard Steinbeck, MD^_*, Ulrich Mansmann, PhD, Annemarie Poustka, PhD, Michael Nabauer, MD^_* and Holger Sültmann, PhD

^_* Department of Medicine I, University Hospital Grosshadern, Munich, Germany
Department of Cardiac Surgery, University Hospital Grosshadern, Munich, Germany
Department of Medical Informatics, Biometrics and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany
^|| Department of Medical Informatics and Biomathematics, University of Münster, Münster, Germany

View larger version (31K): [in this window] [in a new window] [Download PPT slide]   Figure 1 Functional analysis based on Gene Ontology for selected gene classes comparing up-regulated genes in DCM (yellow bars) and down-regulated genes (green bars) in dilated cardiomyopathy (DCM) of datasets A (open bars) and B (striped bars). Differences in gene classes marked by an asterisk were statistically significant (Fisher exact test; p < 0.05) according to "FatiGO" (23). Results for cellular component, biological process, and molecular function are based on (see ).

View larger version (39K): [in this window] [in a new window] [Download PPT slide]   Figure 2 Prediction analysis for microarrays (PAM) classification. In the first step, PAM classification was applied to all 4 datasets separately. Very low misclassification rates were found in datasets A, B, and D for the classification of nonfailing (NF) versus dilated cardiomyopathy (DCM) samples, whereas the classification algorithm did not show any power in dataset C. In the second step, we repeated the procedure with the smallest gene signature obtained from dataset B (31 probe sets which correspond to 27 transcripts), now achieving more than 90% accuracy for classifying DCM and NF samples across all studies, including dataset C.

View larger version (16K): [in this window] [in a new window] [Download PPT slide]   Figure 3 Mean expression ± SEM of pro-brain natriuretic peptide (NPPB) in nonfailing (NF) (black bars) and dilated cardiomyopathy (DCM) samples (red bars) in datasets A to D. Statistical comparison was carried out by Student t test.