novel approach to meta-analysis of microarray datasets reveals muscle remodeling-related drug targets and biomarkers in duchenne muscular dystrophy新颖的方法来分析微阵列数据集显示肌肉remodeling-related药物靶点和生物标志物在杜氏肌萎缩症.pdfVIP

Novel Approach to Meta-Analysis of Microarray Datasets Reveals Muscle Remodeling-related Drug Targets and Biomarkers in Duchenne Muscular Dystrophy 1 1 1 2 Ekaterina Kotelnikova *, Maria A. Shkrob , Mikhail A. Pyatnitskiy , Alessandra Ferlini , Nikolai Daraselia1 1 Ariadne Genomics Inc., Rockville, Maryland, United States of America, 2 Section of Medical Genetics, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy Abstract Elucidation of new biomarkers and potential drug targets from high-throughput profiling data is a challenging task due to a limited number of available biological samples and questionable reproducibility of differential changes in cross-dataset comparisons. In this paper we propose a novel computational approach for drug and biomarkers discovery using comprehensive analysis of multiple expression profiling datasets. The new method relies on aggregation of individual profiling experiments combined with leave-one-dataset-out validation approach. Aggregated datasets were studied using Sub-Network Enrichment Analysis algorithm (SNEA) to find consistent statistically significant key regulators within the global literature-extracted expression regulation network. These regulators were linked to the consistent differentially expressed genes. We have applied our approach to several publicly available human muscle gene expression profiling datasets related to Duchenne muscular dystrophy (DMD). In order to detect both enhanced and repressed processes we considered up- and down-regulated genes separately. Applying the proposed approach to the regulators search we discovered the disturbance