Bioinformatics Group

Richard Mott's Home Page


Mouse Resources

HS QTL Project

QTL mapping with HAPPY

Mouse Haplotype Structure

Complex Trait Consortium Meeting, Oxford 1-3 July 2003

SNP Selection Methods


Domain Localisation

DNA-Protein Binding


Sequence Alignment with ARIADNE

Sequence Alignment with monotonic gap penalties

Aligning an EST to a genomic sequence


BIOSAPIENS Network of Excellence

Integrated Genotyping System (IGS)

 

Wellcome Trust Centre for Human Genetics

DNA-protein Binding Page

This page contains resources related to a project to predict the binding affinity of DNA-Protein interactions, as a function of the DNA sequence. We have developed a new method that identifies interactions between base pair positions in the binding site. It is described in detail here in PNAS (2002) 99:8167-8172. The work is a collaboration with Irina Udalova and Dominic Kwiatkowski .

This page is still under construction.

Abstract

We describe a general method based on principal coordinates analysis to predict the effects of single nucleotide polymorphisms within regulatory sequences on DNA-protein interactions. We use binding data for the transcription factor NF-kB as a test system. The method incorporates the effects of interactions between base pair positions in the binding site, and we demonstrate that such interactions are present for NF-kB. Prediction accuracy is higher than with profile models, confirmed by cross-validation and by the experimental verification of our predictions for additional sequences. The binding affinities of all potential NF-kB sites on human chromosome 22, together with the effects of known SNPs, are calculated to determine likely functional variants. We propose that this approach may be valuable, either on its own or in combination with other methods, when standard profile models are disadvantaged by complex inter-nucleotide interactions.

Download Raw Data (Excel Spreadsheet)

Download R functions to perform analysis (Currently undocumented)

Click here for web server access to software to

  • examine the effect of SNPs on transcription factor binding
  • select the minimum number of DNA sequences to be experimentally assayed for PC model generation
  • generate PC model predictions based on experimental data

Drop me an email for more details.

 
 
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