Modeling within-motif dependence for transcription factor binding site predictions

The position-specific weight matrix (PWM) model, which assumes that each position in the DNA site contributes independently to the overall protein-DNA interaction, has been the primary means to describe transcription factor binding site motifs. Recent biological experiments, however, suggest that there exists interdependence among positions in the binding sites. In order to exploit this interdependence to aid motif discovery, we extend the PWM model to include pairs of correlated positions and design a Markov chain Monte Carlo algorithm to sample in the model space. We then combine the model sampling step with the Gibbs sampling framework for de novo motif discoveries.