Multiple testing of local maxima for detection of peaks in ChIP-Seq data

A topological multiple testing approach to peak detection is proposed for the problem of detecting transcription factor binding sites in ChIP-Seq data. After kernel smoothing of the tag counts over the genome, the presence of a peak is tested at each observed local maximum, followed by multiple testing correction at the desired false discovery rate level. Valid p-values for candidate peaks are computed via Monte Carlo simulations of smoothed Poisson sequences, whose background Poisson rates are obtained via linear regression from a Control sample at two different scales. The proposed method identifies nearby binding sites that other methods do not.