Inferring protein–dna interaction parameters from selex experiments

Abstract

Systematic Evolution of Ligands by EXponential enrichment (SELEX) is an experimental procedure that allows extraction, from an initially random pool of oligonucleotides, of the oligomers with a high binding affinity for a given molecular target. The highest affinity binding sequences isolated through SELEX can have numerous research, diagnostic, and therapeutic applications. Recently, important new modifications of the SELEX protocol have been proposed. In particular, a suitably modified SELEX experiment, together with an appropriate computational procedure, allows inference of protein–DNA interaction parameters with up to now unprecedented accuracy. Such inference is possible even when there is no a priori information on transcription factor binding specificity, which allows accurate predictions of binding sites for any transcription factor of interest. In this chapter we discuss how to accurately determine protein–DNA interaction parameters from SELEX experiments. The chapter addresses experimental and computational procedure needed to generate and analyze appropriate data.