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Identifying cooperative transcription factors in yeast using multiple data sources.

Lai FJ, Jhu MH, Chiu CC, Huang YM, Wu WS - BMC Syst Biol (2014)

Bottom Line: Our method is effective in identifying cooperative TF pairs in yeast.Many of our predictions are validated by the literature, and our method outperforms 11 existing methods.We believe that our study will help biologists to understand the mechanisms of transcriptional regulation in eukaryotic cells.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Transcriptional regulation of gene expression is usually accomplished by multiple interactive transcription factors (TFs). Therefore, it is crucial to understand the precise cooperative interactions among TFs. Various kinds of experimental data including ChIP-chip, TF binding site (TFBS), gene expression, TF knockout and protein-protein interaction data have been used to identify cooperative TF pairs in existing methods. The nucleosome occupancy data is not yet used for this research topic despite that several researches have revealed the association between nucleosomes and TFBSs.

Results: In this study, we developed a novel method to infer the cooperativity between two TFs by integrating the TF-gene documented regulation, TFBS and nucleosome occupancy data. TF-gene documented regulation and TFBS data were used to determine the target genes of a TF, and the genome-wide nucleosome occupancy data was used to assess the nucleosome occupancy on TFBSs. Our method identifies cooperative TF pairs based on two biologically plausible assumptions. If two TFs cooperate, then (i) they should have a significantly higher number of common target genes than random expectation and (ii) their binding sites (in the promoters of their common target genes) should tend to be co-depleted of nucleosomes in order to make these binding sites simultaneously accessible to TF binding. Each TF pair is given a cooperativity score by our method. The higher the score is, the more likely a TF pair has cooperativity. Finally, a list of 27 cooperative TF pairs has been predicted by our method. Among these 27 TF pairs, 19 pairs are also predicted by existing methods. The other 8 pairs are novel cooperative TF pairs predicted by our method. The biological relevance of these 8 novel cooperative TF pairs is justified by the existence of protein-protein interactions and co-annotation in the same MIPS functional categories. Moreover, we adopted three performance indices to compare our predictions with 11 existing methods' predictions. We show that our method performs better than these 11 existing methods in identifying cooperative TF pairs in yeast. Finally, the cooperative TF network constructed from the 27 predicted cooperative TF pairs shows that our method has the power to find cooperative TF pairs of different biological processes.

Conclusion: Our method is effective in identifying cooperative TF pairs in yeast. Many of our predictions are validated by the literature, and our method outperforms 11 existing methods. We believe that our study will help biologists to understand the mechanisms of transcriptional regulation in eukaryotic cells.

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Comparison of our method with 11 existing methods based on the precision and recall when using a benchmark set of 27 known cooperative TF pairs. Here, we use the precision and recall to evaluate the performance of a method. The figure shows that our method outperforms 11 existing methods in the precision and outperforms 10 existing methdos in the recall.
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Figure 5: Comparison of our method with 11 existing methods based on the precision and recall when using a benchmark set of 27 known cooperative TF pairs. Here, we use the precision and recall to evaluate the performance of a method. The figure shows that our method outperforms 11 existing methods in the precision and outperforms 10 existing methdos in the recall.

Mentions: In the performance index 3, the significance of the overlap of the list of PCTFPs from a method with the benchmark set of 27 known cooperative TF pairs is used to evaluate the performance of a method. Here, we use the precision and recall to evaluate the performance of a method. As shown in Figure 5, our method outperforms 11 existing methods in the precision and outperforms 10 existing methods in the recall.


Identifying cooperative transcription factors in yeast using multiple data sources.

Lai FJ, Jhu MH, Chiu CC, Huang YM, Wu WS - BMC Syst Biol (2014)

Comparison of our method with 11 existing methods based on the precision and recall when using a benchmark set of 27 known cooperative TF pairs. Here, we use the precision and recall to evaluate the performance of a method. The figure shows that our method outperforms 11 existing methods in the precision and outperforms 10 existing methdos in the recall.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4305981&req=5

Figure 5: Comparison of our method with 11 existing methods based on the precision and recall when using a benchmark set of 27 known cooperative TF pairs. Here, we use the precision and recall to evaluate the performance of a method. The figure shows that our method outperforms 11 existing methods in the precision and outperforms 10 existing methdos in the recall.
Mentions: In the performance index 3, the significance of the overlap of the list of PCTFPs from a method with the benchmark set of 27 known cooperative TF pairs is used to evaluate the performance of a method. Here, we use the precision and recall to evaluate the performance of a method. As shown in Figure 5, our method outperforms 11 existing methods in the precision and outperforms 10 existing methods in the recall.

Bottom Line: Our method is effective in identifying cooperative TF pairs in yeast.Many of our predictions are validated by the literature, and our method outperforms 11 existing methods.We believe that our study will help biologists to understand the mechanisms of transcriptional regulation in eukaryotic cells.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Transcriptional regulation of gene expression is usually accomplished by multiple interactive transcription factors (TFs). Therefore, it is crucial to understand the precise cooperative interactions among TFs. Various kinds of experimental data including ChIP-chip, TF binding site (TFBS), gene expression, TF knockout and protein-protein interaction data have been used to identify cooperative TF pairs in existing methods. The nucleosome occupancy data is not yet used for this research topic despite that several researches have revealed the association between nucleosomes and TFBSs.

Results: In this study, we developed a novel method to infer the cooperativity between two TFs by integrating the TF-gene documented regulation, TFBS and nucleosome occupancy data. TF-gene documented regulation and TFBS data were used to determine the target genes of a TF, and the genome-wide nucleosome occupancy data was used to assess the nucleosome occupancy on TFBSs. Our method identifies cooperative TF pairs based on two biologically plausible assumptions. If two TFs cooperate, then (i) they should have a significantly higher number of common target genes than random expectation and (ii) their binding sites (in the promoters of their common target genes) should tend to be co-depleted of nucleosomes in order to make these binding sites simultaneously accessible to TF binding. Each TF pair is given a cooperativity score by our method. The higher the score is, the more likely a TF pair has cooperativity. Finally, a list of 27 cooperative TF pairs has been predicted by our method. Among these 27 TF pairs, 19 pairs are also predicted by existing methods. The other 8 pairs are novel cooperative TF pairs predicted by our method. The biological relevance of these 8 novel cooperative TF pairs is justified by the existence of protein-protein interactions and co-annotation in the same MIPS functional categories. Moreover, we adopted three performance indices to compare our predictions with 11 existing methods' predictions. We show that our method performs better than these 11 existing methods in identifying cooperative TF pairs in yeast. Finally, the cooperative TF network constructed from the 27 predicted cooperative TF pairs shows that our method has the power to find cooperative TF pairs of different biological processes.

Conclusion: Our method is effective in identifying cooperative TF pairs in yeast. Many of our predictions are validated by the literature, and our method outperforms 11 existing methods. We believe that our study will help biologists to understand the mechanisms of transcriptional regulation in eukaryotic cells.

Show MeSH
Related in: MedlinePlus