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p53 pathway responds to various cellular stress signals (the input) by activating p53 as a transcription factor (increasing its levels and protein modifications) and transcribing a programme of genes (the output) to accomplish a number of functions (FIG. 1). Together, these functions prevent errors in the duplication process of a cell that is under stress,(More)
Genomic analyses often involve scanning for potential transcription factor (TF) binding sites using models of the sequence specificity of DNA binding proteins. Many approaches have been developed to model and learn a protein's DNA-binding specificity, but these methods have not been systematically compared. Here we applied 26 such approaches to in vitro(More)
Members of transcription factor families typically have similar DNA binding specificities yet execute unique functions in vivo. Transcription factors often bind DNA as multiprotein complexes, raising the possibility that complex formation might modify their DNA binding specificities. To test this hypothesis, we developed an experimental and computational(More)
DNA binding proteins find their cognate sequences within genomic DNA through recognition of specific chemical and structural features. Here we demonstrate that high-resolution DNase I cleavage profiles can provide detailed information about the shape and chemical modification status of genomic DNA. Analyzing millions of DNA backbone hydrolysis events on(More)
BACKGROUND A computational method (called p53HMM) is presented that utilizes Profile Hidden Markov Models (PHMMs) to estimate the relative binding affinities of putative p53 response elements (REs), both p53 single-sites and cluster-sites. These models incorporate a novel "Corresponded Baum-Welch" training algorithm that provides increased predictive power(More)
Transcription factors are crucial regulators of gene expression. Accurate quantitative definition of their intrinsic DNA binding preferences is critical to understanding their biological function. High-throughput in vitro technology has recently been used to deeply probe the DNA binding specificity of hundreds of eukaryotic transcription factors, yet(More)
  • Todd Riley, Xin Yu, Eduardo Sontag, Arnold Levine
  • 2009
Given a set S of experimentally validated binding sites s for a TF-protein (and a few assumptions) it is possible to use the set S to estimate the relative binding free energy −∆G(x) of any putative site x (without having to perform direct experimental measurements of binding constants). This bioinformatic approach using PHMMs (and PSSMs) is an attractive(More)
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