Probabilistic peak calling and controlling false discovery rate estimations in transcription factor binding site mapping from ChIP-seq.

Localizing the binding sites of regulatory proteins is becoming increasingly feasible and accurate. This is due to dramatic progress not only in chromatin immunoprecipitation combined by next-generation sequencing (ChIP-seq) but also in advanced statistical analyses. A fundamental issue, however, is the alarming number of false positive predictions. This problem can be remedied by improved peak calling methods of twin peaks, one at each strand of the DNA, kernel density estimators, and false discovery rate estimations based on control libraries. Predictions are filtered by de novo motif discovery in the peak environments. These methods have been implemented in, among others, Valouev et al.'s Quantitative Enrichment of Sequence Tags (QuEST) software tool. We demonstrate the prediction of the human growth-associated binding protein (GABPalpha) based on ChIP-seq observations.