title: A latent variable model for chemogenomic profiling.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  Supplementary information and computer code at http://genomics.lbl.gov/llda.
authors.affiliation: Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA 94720, USA. flaherty@berkeley.edu
authors.forename: Patrick
authors.initials: P
authors.lastname: Flaherty
authors.forename: Guri
authors.initials: G
authors.lastname: Giaever
authors.forename: Jochen
authors.initials: J
authors.lastname: Kumm
authors.forename: Michael I
authors.initials: MI
authors.lastname: Jordan
authors.forename: Adam P
authors.initials: AP
authors.lastname: Arkin
mesh_terms: D003198:Computer Simulation; D017353:Gene Deletion; D020869:Gene Expression Profiling / Q000379:methods*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000502:physiology*; D008957:Models, Genetic; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010597:Pharmacogenetics / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D029701:Saccharomyces cerevisiae Proteins