Large-scale gene expression data comprising a variety of cellular conditions hold the promise of a global view on the transcription program. While conventional clustering algorithms have been successfully applied to smaller datasets, the utility of many algorithms for the analysis of large-scale data is limited by their inability to capture combinatorial and condition-specific co-regulation. In addition, there is an increasing need to integrate the rapidly accumulating body of other high-throughput biological data with the expression analysis. In a previous work, we introduced the signature algorithm, which overcomes the problems of conventional clustering and allows for intuitive integration of additional biological data. However, this approach is constrained by the comprehensiveness of relevant external data and its lacking ability to capture hierarchical modularity.