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Computational analysis of muscular dystrophy sub-types using a novel integrative scheme

Authors
Journal
Neurocomputing
0925-2312
Publisher
Elsevier
Publication Date
Volume
92
Identifiers
DOI: 10.1016/j.neucom.2011.08.037
Keywords
  • Gene Expression
  • Classification
  • Muscular Dystrophy
  • Affinity Propagation Clustering
  • Biomarker Discovery
Disciplines
  • Biology
  • Computer Science

Abstract

Abstract To construct biologically interpretable gene sets for muscular dystrophy (MD) sub-type classification, we propose a novel computational scheme to integrate protein–protein interaction (PPI) network, functional gene set information, and mRNA profiling data. The workflow of the proposed scheme includes the following three major steps: firstly, we apply an affinity propagation clustering (APC) approach to identify gene sub-networks associated with each MD sub-type, in which a new distance metric is proposed for APC to combine PPI network information and gene–gene co-expression relationship; secondly, we further incorporate functional gene set knowledge, which complements the physical PPI information, into our scheme for biomarker identification; finally, based on the constructed sub-networks and gene set features, we apply multiclass support vector machines (MSVMs) for MD sub-type classification, with which to highlight the biomarkers contributing to sub-type prediction. The experimental results show that our scheme can help identify sub-networks and gene sets that are more relevant to MD than those constructed by other conventional approaches. Moreover, our integrative strategy improves the prediction accuracy substantially, especially for those ‘hard-to-classify’ sub-types.

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