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.

• PMID: 15919724
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Evaluation Study | Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.

Authors

Flaherty P, Giaever G, Kumm J, Jordan MI, Arkin AP

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