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Background  Gene expression and transcription factor (TF) binding data have been used to reveal gene transcriptional regulatory networks. Existing knowledge of gene regulation can be presented using gene connectivity networks. However, these composite connectivity networks do not specify the range of biological conditions of the activity of each link in the network.    Results  We present a novel method that utilizes the expression and binding patterns of the neighboring nodes of each link in existing experimentally-based, literature-derived gene transcriptional regulatory networks and extend them  in silico  using TF-gene binding motifs and a compendium of large expression data from  Saccharomyces cerevisiae . Using this method, we predict several hundreds of new transcriptional regulatory TF-gene links, along with experimental conditions in which known and predicted links become active. This approach unravels new links in the yeast gene transcriptional regulatory network by utilizing the known transcriptional regulatory interactions, and is particularly useful for breaking down the composite transcriptional regulatory network to condition specific networks.    Conclusion  Our methods can facilitate future binding experiments, as they can considerably help focus on the TFs that must be surveyed to understand gene regulation.  (Supplemental material and the latest version of the MATLAB implementation of the United Signature Algorithm is available online at [ 1 ] or [see Additional files  1 ,  2 ,  3 ,  4 ,  5 ,  6 ,  7 ,  8 ,  9 ,  10 ])

Unraveling condition specific gene transcriptional regulatory networks in Saccharomyces cerevisiae