A methodology based on molecular interactions and pathways to find candidate genes associated to diseases: its application to schizophrenia and Alzheimer's disease

J Bioinform Comput Biol. 2011 Aug;9(4):541-57. doi: 10.1142/s0219720011005392.

Abstract

Experimental techniques for the identification of genes associated with diseases are expensive and have certain limitations. In this scenario, computational methods are useful tools to identify lists of promising genes for further experimental verification. This paper describes a flexible methodology for the in silico prediction of genes associated with diseases combining the use of available tools for gene enrichment analysis, gene network generation and gene prioritization. A set of reference genes, with a known association to a disease, is used as bait to extract candidate genes from molecular interaction networks and enriched pathways. In a second step, prioritization methods are applied to evaluate the similarities between previously selected candidates and the set of reference genes. The top genes obtained by these programs are grouped into a single list sorted by the number of methods that have selected each gene. As a proof of concept, top genes reported a few years ago in SzGene and AlzGene databases were used as references to predict genes associated to schizophrenia and Alzheimer's disease, respectively. In both cases, we were able to predict a statistically significant amount of genes belonging to the updated lists.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Computational Biology
  • Databases, Genetic
  • Gene Regulatory Networks
  • Genetic Association Studies / statistics & numerical data*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / statistics & numerical data
  • Humans
  • Schizophrenia / genetics*
  • Software Design