By crosslinking the in vivo DNA–protein complexes using formaldehyde, sonicating to break the DNA, precipitating the protein of interest using a specific antibody, reversing the crosslinks, sequencing the DNA fragments and mapping them to a reference genome, a genome-wide map of TFBS with a resolution of 100–200 bp can be obtained. THiCweed thus goes beyond traditional motif finding to give new insights into genomic transcription factor-binding complexity.Ĭhromatin immunoprecipitation with sequencing (ChIP-seq) ( 1) is a widely used assay for determining transcription factor-binding sites (TFBS) in vivo.

We also find recurring sequence patterns across diverse ChIP-seq datasets, possibly related to chromatin architecture and looping. On real data it successfully recovers literature motifs, but also uncovers complex sequence characteristics in flanking DNA, variant motifs and secondary motifs even when they occur in <5% of the input, all of which appear biologically relevant. THiCweed performs best with large ‘window’ sizes (≥50 bp), much longer than typical binding sites (7–15 bp). On synthetic data containing mixtures of motifs it is as accurate or more accurate than all other tested programs. Our implementation is significantly faster than standard motif-finding programs, able to process 30 000 peaks in 1–2 h, on a single CPU core of a desktop computer. ThiCweed is specially geared toward data containing mixtures of motifs, which present a challenge to traditional motif-finders. THiCweed clusters bound regions based on sequence similarity using a divisive hierarchical clustering approach based on sequence similarity within sliding windows, while exploring both strands. We present THiCweed, a new approach to analyzing transcription factor binding data from high-throughput chromatin immunoprecipitation-sequencing (ChIP-seq) experiments. THiCweed thus goes beyond traditional motif finding to give new insights into genomic transcription factor-binding complexity. THiCweed performs best with large 'window' sizes (≥50 bp), much longer than typical binding sites (7-15 bp). Our implementation is significantly faster than standard motif-finding programs, able to process 30 000 peaks in 1-2 h, on a single CPU core of a desktop computer.

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