Modeling protein–DNA binding via high-throughputin vitrotechnologies

Protein-DNA binding plays a central role in gene regulation and by that in all processes in the living cell. Novel experimental and computational approaches facilitate better understanding of protein-DNA binding preferences via high-throughput measurement of protein binding to a large number of DNA sequences and inference of binding models from them. Here we review the state of the art in measuring protein-DNA binding in vitro, emphasizing the advantages and limitations of different technologies. In addition, we describe models for representing protein-DNA binding preferences and key computational approaches to learn those from high-throughput data. Using large experimental data sets, we test the performance of different models based on different measuring techniques. We conclude with pertinent open problems.