Incorporating Motif Discovery in Investigation of Transcription Factor Cooperativity in Saccharomyces Cerevisiae
Date Issued
2009
Date
2009
Author(s)
Chen, Mei-Ju
Abstract
Transcriptional regulation typically happens after the binding of transcription factors (TFs) to the specific promoter regions of their target genes. TFs frequently regulate gene expression by cooperating with other TFs. Recent advances in high-throughput tools, e.g. Chromatin immunoprecipitation chip (ChIP-chip) and microarray expression data, provides us with considerable information to investigate transcription regulatory modules (TRMs), or groups of cooperative TFs. Many recent studies have developed computational methods to study TF cooperativity by utilizing ChIP-chip data alone or integrating information from both ChIP-chip and microarray data. Since methods employing gene expression information highly rely on the availability and quality of microarray data, this thesis proposes a method named simTFBS, which uses ChIP-chip data alone but incorporating pattern discovery and analysis procedures when finding potential cooperative TF pairs. The proposed method first identifies potential target genes for each TF based on the ChIP-chip data. After that, a previously developed algorithm for predicting TF binding sites (TFBSs) is applied on each TF to derive a top-10 list of potential TFBSs. For a pair of TFs with at least one common target gene, we check whether their top-10 pattern lists share at least one pair of similar TFBSs which suggest cooperativity. Finally, each TF pair is given a score representing the degree of cooperativity defined by the mutual information score between respective target gene lists. In this thesis, the answer set for evaluation is built by collecting known protein-protein interactions (PPI) from databases and annotated synergy relationships from literatures. The results reveal that the proposed approach performs better than many existing methods and also helps to associate a potential TRM with the related TFBSs when constructing gene regulatory networks.
Subjects
Saccharomyces Cerevisiae
transcriptional regulation
transcription factor cooperativity
transcription regulatory module
motif discovery
transcription factor binding site
Chromatin immunoprecipitation chip
Type
thesis
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