A latent variable model for chemogenomic profiling

Bioinformatics. 2005 Aug 1;21(15):3286-93. doi: 10.1093/bioinformatics/bti515. Epub 2005 May 26.

Abstract

Motivation: In haploinsufficiency profiling data, pleiotropic genes are often misclassified by clustering algorithms that impose the constraint that a gene or experiment belong to only one cluster. We have developed a general probabilistic model that clusters genes and experiments without requiring that a given gene or drug only appear in one cluster. The model also incorporates the functional annotation of known genes to guide the clustering procedure.

Results: We applied our model to the clustering of 79 chemogenomic experiments in yeast. Known pleiotropic genes PDR5 and MAL11 are more accurately represented by the model than by a clustering procedure that requires genes to belong to a single cluster. Drugs such as miconazole and fenpropimorph that have different targets but similar off-target genes are clustered more accurately by the model-based framework. We show that this model is useful for summarizing the relationship among treatments and genes affected by those treatments in a compendium of microarray profiles.

Availability: Supplementary information and computer code at http://genomics.lbl.gov/llda.

Publication types

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

MeSH terms

  • Computer Simulation
  • Gene Deletion
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Fungal / drug effects
  • Gene Expression Regulation, Fungal / physiology*
  • Models, Genetic*
  • Models, Statistical
  • Oligonucleotide Array Sequence Analysis / methods*
  • Pharmaceutical Preparations / administration & dosage
  • Pharmacogenetics / methods*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Pharmaceutical Preparations
  • Saccharomyces cerevisiae Proteins