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laboratory

 

p53HMM

The tumor-suppressor protein p53 predominantly binds as a tetramer to a canonical halfsite-spacer-halfsite motif, where each 10bp halfsite is highly degenerate. Using a dataset of 160 experimentally validated, functional, human p53 binding sites, I have shown that p53 binding affinities are highly influenced by the spacer length, by long-range dependencies between nucleotide positions, and by nucleotide insertions and deletions often tolerated within the half-sites (Riley et al., Nat Rev Mol Cell Biol, 2008).

I also discovered that the lower-bound for the binding affinity of functional p53 binding sites is directly related to their distance from the transcription start site (TSS), and that the false positive rate for finding functional p53 binding sites can be greatly reduced by using a dynamic binding-affinity acceptance threshold that is dependent upon the putative site's distance from the TSS (Riley et al., BMC Bioinformatics, 2009).

The p53HMM tool that integrates these observations into a p53-motif search tool in an Hidden Markov Model (HMM) framework will soon be available online again.

A link to our Nat Rev Mol Cell Biol paper is here.
A link to our BMC Bioinformatics paper is here.