  The solution of high-dimensional inference and prediction problems in
computational biology is almost always a compromise between mathematical theory
and practical constraints such as limited computational resources. As time
progresses, computational power increases but well-established inference
methods often remain locked in their initial suboptimal solution. We revisit
the approach of Segal et al. (2003) to infer regulatory modules and their
condition-specific regulators from gene expression data. In contrast to their
direct optimization-based solution we use a more representative centroid-like
solution extracted from an ensemble of possible statistical models to explain
the data. The ensemble method automatically selects a subset of most
informative genes and builds a quantitatively better model for them. Genes
which cluster together in the majority of models produce functionally more
coherent modules. Regulators which are consistently assigned to a module are
more often supported by literature, but a single model always contains many
regulator assignments not supported by the ensemble. Reliably detecting
condition-specific or combinatorial regulation is particularly hard in a single
optimum but can be achieved using ensemble averaging.
