Effective classification and gene expression profiling for the Facioscapulohumeral Muscular Dystrophy

  • Gonzalez-Navarro F
  • Belanche-Munoz L
  • Silva-Colon K
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Abstract

The Facioscapulohumeral Muscular Dystrophy (FSHD) is an autosomal dominant neuromuscular disorder whose incidence is estimated in about one in 400,000 to one in 20,000. No effective therapeutic strategies are known to halt progression or reverse muscle weakness and atrophy. It is known that the FSHD is caused by modifications located within a D4ZA repeat array in the chromosome 4q, while recent advances have linked these modifications to the DUX4 gene. Unfortunately, the complete mechanisms responsible for the molecular pathogenesis and progressive muscle weakness still remain unknown. Although there are many studies addressing cancer databases from a machine learning perspective, there is no such precedent in the analysis of the FSHD. This study aims to fill this gap by analyzing two specific FSHD databases. A feature selection algorithm is used as the main engine to select genes promoting the highest possible classification capacity. The combination of feature selection and classification aims at obtaining simple models (in terms of very low numbers of genes) capable of good generalization, that may be associated with the disease. We show that the reported method is highly efficient in finding genes to discern between healthy cases (not affected by the FSHD) and FSHD cases, allowing the discovery of very parsimonious models that yield negligible repeated cross-validation error. These models in turn give rise to very simple decision procedures in the form of a decision tree. Current biological evidence regarding these genes shows that they are linked to skeletal muscle processes concerning specific human conditions.

Author-supplied keywords

  • *Gene Expression Profiling
  • Algorithms
  • Cluster Analysis
  • Databases, Genetic
  • Gene Expression Regulation
  • Humans
  • Models, Genetic
  • Muscular Dystrophy, Facioscapulohumeral/*classific

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Authors

  • F F Gonzalez-Navarro

  • L A Belanche-Munoz

  • K A Silva-Colon

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