A latent variable model for chemogenomic profiling.
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.
Flaherty
Patrick
P
Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA 94720, USA. flaherty@berkeley.edu
Giaever
Guri
G
Kumm
Jochen
J
Jordan
Michael I
MI
Arkin
Adam P
AP
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*
D004364:Pharmaceutical Preparations; D029701:Saccharomyces cerevisiae Proteins