Unraveling condition specific gene transcriptional regulatory networks in <it>Saccharomyces cerevisiae</it>

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 <it>in silico </it>using TF-gene binding motifs and a compendium of large expression data from <it>Saccharomyces cerevisiae</it>. 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.</p> <p>Conclusion</p> <p>Our methods can facilitate future binding experiments, as they can considerably help focus on the TFs that must be surveyed to understand gene regulation.</p> <p>(Supplemental material and the latest version of the MATLAB implementation of the United Signature Algorithm is available online at <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> or [see Additional files <supplr sid="S1">1</supplr>, <supplr sid="S2">2</supplr>, <supplr sid="S3">3</supplr>, <supplr sid="S4">4</supplr>, <supplr sid="S5">5</supplr>, <supplr sid="S6">6</supplr>, <supplr sid="S7">7</supplr>, <supplr sid="S8">8</supplr>, <supplr sid="S9">9</supplr>, <supplr sid="S10">10</supplr>])</p> <suppl id="S1"> <title> <p>Additional File 1</p> </title> <text> <p>overview of supplemental data</p> </text> <file name="1471-2105-7-165-S1.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S2"> <title> <p>Additional File 2</p> </title> <text> <p>experimental conditions for each link in figure <figr fid="F5">5</figr>. These are the experimental conditions in which the links are likely to be active.</p> </text> <file name="1471-2105-7-165-S2.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S3"> <title> <p>Additional File 3</p> </title> <text> <p>experimental conditions for each link in figure <figr fid="F7">7</figr>. These are the experimental conditions in which the links are likely to be active.</p> </text> <file name="1471-2105-7-165-S3.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S4"> <title> <p>Additional File 4</p> </title> <text> <p>Alon's transcriptional regulatory sub-network. Sparse representation of the Alon's network where column one represents the TF and column two represents the target. Entry of 1(2) corresponds to activation (suppression)</p> </text> <file name="1471-2105-7-165-S4.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S5"> <title> <p>Additional File 5</p> </title> <text> <p>The Union of Alon's and Palsson's transcriptional regulatory sub-networks. Sparse representation of this unified network where column one represents the TF and column two represents the target. Entry of 1(2) corresponds to activation (suppression)</p> </text> <file name="1471-2105-7-165-S5.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S6"> <title> <p>Additional File 6</p> </title> <text> <p>Predicted transcriptional regulatory links obtained by applying the LINK model to Alon's network. Each link is accompanied by a list of experiments in which it is likely to be functional.</p> </text> <file name="1471-2105-7-165-S6.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S7"> <title> <p>Additional File 7</p> </title> <text> <p>Predicted transcriptional regulatory links obtained by applying the LINK model to the combined network obtained by unifying Alon's and Palsson's networks. Each link is accompanied by a list of experiments in which it is likely to be functional.</p> </text> <file name="1471-2105-7-165-S7.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S8"> <title> <p>Additional File 8</p> </title> <text> <p>Predicted transcriptional regulatory links obtained by applying the STAR model to Alon's network. Each link is accompanied by a list of experiments in which it is likely to be functional.</p> </text> <file name="1471-2105-7-165-S8.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S9"> <title> <p>Additional File 9</p> </title> <text> <p>Predicted transcriptional regulatory links obtained by applying the STAR model to the combined network obtained by unifying Alon's and Palsson's networks. Each link is accompanied by a list of experiments in which it is likely to be functional.</p> </text> <file name="1471-2105-7-165-S9.pdf"> <p>Click here for file</p> </file> </suppl> <suppl id="S10"> <title> <p>Additional File 10</p> </title> <text> <p>Exploring the parameter space. Overlap between our condition specific predicted networks and condition specific ChIP-on-chip data.</p> </text> <file name="1471-2105-7-165-S10.pdf"> <p>Click here for file</p> </file> </suppl>