Evaluation and integration of 49 genome-wide experiments and the prediction of previously unknown obesity-related genes

Bioinformatics. 2007 Nov 1;23(21):2910-7. doi: 10.1093/bioinformatics/btm483. Epub 2007 Oct 5.

Abstract

Motivation: Genome-wide experiments only rarely show resounding success in yielding genes associated with complex polygenic disorders. We evaluate 49 obesity-related genome-wide experiments with publicly available findings including microarray, genetics, proteomics and gene knock-down from human, mouse, rat and worm, in terms of their ability to rediscover a comprehensive set of genes previously found to be causally associated or having variants associated with obesity.

Results: Individual experiments show poor predictive ability for rediscovering known obesity-associated genes. We show that intersecting the results of experiments significantly improves the sensitivity, specificity and precision of the prediction of obesity-associated genes. We create an integrative model that statistically significantly outperforms all 49 individual genome-wide experiments. We find that genes known to be associated with obesity are significantly implicated in more obesity-related experiments and use this to provide a list of genes that we predict to have the highest likelihood of association for obesity. The approach described here can include any number and type of genome-wide experiments and might be useful for other complex polygenic disorders as well.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Biomarkers / metabolism
  • Chromosome Mapping / methods*
  • Databases, Protein*
  • Gene Expression Profiling / methods*
  • Humans
  • Information Storage and Retrieval / methods
  • Obesity / metabolism*
  • Proteome / metabolism*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Systems Integration

Substances

  • Biomarkers
  • Proteome