SELEX-seq
In collaboration with the Mann Lab, I worked to pioneer a new in vitro high-throughput protocol to determine the sequence specificity of TF-DNA complexes and achieved a quantification of relative binding affinities at an unprecedented level of accuracy (Slattery, Riley et al., Cell, 2011).
Our new SELEX-seq method combines classical protein-DNA SELEX (Systematic Evolution of Ligands by EXponential Enrichment) assays with massively parallel sequencing. Our biophysical model accounts for potential biases in the initial pool of dsDNA oligos, and includes two separate inference methods to generate replicate affinity models that can be compared for quality assurance. One inference method uses LOESS regression methods to integrate the read counts from early and late SELEX rounds, while the other uses poisson regression methods with the read counts from only the first round.
A link to our Cell paper is here.