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Characterizing regulatory path motifs in integrated networks using perturbational data.

Joshi A, Van Parys T, Peer YV, Michoel T - Genome Biol. (2010)

Bottom Line: We introduce Pathicular http://bioinformatics.psb.ugent.be/software/details/Pathicular, a Cytoscape plugin for studying the cellular response to perturbations of transcription factors by integrating perturbational expression data with transcriptional, protein-protein and phosphorylation networks.Pathicular searches for 'regulatory path motifs', short paths in the integrated physical networks which occur significantly more often than expected between transcription factors and their targets in the perturbational data.A case study in Saccharomyces cerevisiae identifies eight regulatory path motifs and demonstrates their biological significance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Plant Systems Biology, VIB, Technologiepark 927, Gent, Belgium. anagha.joshi@psb.vib-ugent.be

ABSTRACT
We introduce Pathicular http://bioinformatics.psb.ugent.be/software/details/Pathicular, a Cytoscape plugin for studying the cellular response to perturbations of transcription factors by integrating perturbational expression data with transcriptional, protein-protein and phosphorylation networks. Pathicular searches for 'regulatory path motifs', short paths in the integrated physical networks which occur significantly more often than expected between transcription factors and their targets in the perturbational data. A case study in Saccharomyces cerevisiae identifies eight regulatory path motifs and demonstrates their biological significance.

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Regulatory path motifs. List of eight enriched regulatory path motifs in deletion and over-expression data, showing five paths common to both. Path motifs are at the center while at the sides an example in each data set is shown. TRI are in red, PPI in blue and PhI in green. The dashed gray edges represent coexpression links while pink and orange edges represent deletion and overexpression links respectively.
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Figure 3: Regulatory path motifs. List of eight enriched regulatory path motifs in deletion and over-expression data, showing five paths common to both. Path motifs are at the center while at the sides an example in each data set is shown. TRI are in red, PPI in blue and PhI in green. The dashed gray edges represent coexpression links while pink and orange edges represent deletion and overexpression links respectively.

Mentions: Out of all 39 possible paths of length up to three in the integrated TRI-PPI-PhI network, eight were significantly enriched (Table 1 and Figure 3). Five regulatory path motifs were overrepresented in both the deletion and overexpression data, namely TRI, TRI-TRI, PPI-TRI, PPI-TRI-TRI and PPI-PhI-TRI. One regulatory path motif, TRI-PPI, was overrepresented only in the deletion data, while two, TRI-PhI-TRI and TRI-PPI-TRI, were overrepresented only in the overexpression data. To check the robustness of these results, we created integrated networks obtained from different sources and using different p-value cutoffs (see Methods and Tables S6 and S7 in Additional File 1 for details). We also confirmed that the regulatory path motifs were not enriched because of the presence of previously well characterized overrepresented network motifs in the static network [12,13,25]. For instance, a feed-forward loop is formed by a combination of a TRI and a TRI-TRI path. We checked the enrichment of all indirect paths by removing indirect paths when also a direct path (TRI) is present, and the results still hold true. This shows that the regulatory path motifs are all significant signals independent of the simple TRI enrichment.


Characterizing regulatory path motifs in integrated networks using perturbational data.

Joshi A, Van Parys T, Peer YV, Michoel T - Genome Biol. (2010)

Regulatory path motifs. List of eight enriched regulatory path motifs in deletion and over-expression data, showing five paths common to both. Path motifs are at the center while at the sides an example in each data set is shown. TRI are in red, PPI in blue and PhI in green. The dashed gray edges represent coexpression links while pink and orange edges represent deletion and overexpression links respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2864572&req=5

Figure 3: Regulatory path motifs. List of eight enriched regulatory path motifs in deletion and over-expression data, showing five paths common to both. Path motifs are at the center while at the sides an example in each data set is shown. TRI are in red, PPI in blue and PhI in green. The dashed gray edges represent coexpression links while pink and orange edges represent deletion and overexpression links respectively.
Mentions: Out of all 39 possible paths of length up to three in the integrated TRI-PPI-PhI network, eight were significantly enriched (Table 1 and Figure 3). Five regulatory path motifs were overrepresented in both the deletion and overexpression data, namely TRI, TRI-TRI, PPI-TRI, PPI-TRI-TRI and PPI-PhI-TRI. One regulatory path motif, TRI-PPI, was overrepresented only in the deletion data, while two, TRI-PhI-TRI and TRI-PPI-TRI, were overrepresented only in the overexpression data. To check the robustness of these results, we created integrated networks obtained from different sources and using different p-value cutoffs (see Methods and Tables S6 and S7 in Additional File 1 for details). We also confirmed that the regulatory path motifs were not enriched because of the presence of previously well characterized overrepresented network motifs in the static network [12,13,25]. For instance, a feed-forward loop is formed by a combination of a TRI and a TRI-TRI path. We checked the enrichment of all indirect paths by removing indirect paths when also a direct path (TRI) is present, and the results still hold true. This shows that the regulatory path motifs are all significant signals independent of the simple TRI enrichment.

Bottom Line: We introduce Pathicular http://bioinformatics.psb.ugent.be/software/details/Pathicular, a Cytoscape plugin for studying the cellular response to perturbations of transcription factors by integrating perturbational expression data with transcriptional, protein-protein and phosphorylation networks.Pathicular searches for 'regulatory path motifs', short paths in the integrated physical networks which occur significantly more often than expected between transcription factors and their targets in the perturbational data.A case study in Saccharomyces cerevisiae identifies eight regulatory path motifs and demonstrates their biological significance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Plant Systems Biology, VIB, Technologiepark 927, Gent, Belgium. anagha.joshi@psb.vib-ugent.be

ABSTRACT
We introduce Pathicular http://bioinformatics.psb.ugent.be/software/details/Pathicular, a Cytoscape plugin for studying the cellular response to perturbations of transcription factors by integrating perturbational expression data with transcriptional, protein-protein and phosphorylation networks. Pathicular searches for 'regulatory path motifs', short paths in the integrated physical networks which occur significantly more often than expected between transcription factors and their targets in the perturbational data. A case study in Saccharomyces cerevisiae identifies eight regulatory path motifs and demonstrates their biological significance.

Show MeSH