THiCweed: fast, sensitive detection of sequence features by clustering big datasets

TitleTHiCweed: fast, sensitive detection of sequence features by clustering big datasets
Publication TypeJournal Article
Year of Publication2018
AuthorsAgrawal, A, Sambare, SV, Narlikar, L, Siddharthan, R
JournalNucleic Acids Research
Volume46
Issue5
Paginatione29
Date PublishedMAR
ISSN0305-1048
Abstract

We present THiCweed, a new approach to analyzing transcription factor binding data from high-throughput chromatin immunoprecipitation-sequencing (ChIP-seq) experiments. 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. ThiCweed is specially geared toward data containing mixtures of motifs, which present a challenge to traditional motif-finders. 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. On synthetic data containing mixtures of motifs it is as accurate or more accurate than all other tested programs. THiCweed performs best with large `window' sizes (>50 bp), much longer than typical binding sites (7-15 bp). 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. We also find recurring sequence patterns across diverse ChIP-seq datasets, possibly related to chromatin architecture and looping. THiCweed thus goes beyond traditional motif finding to give new insights into genomic transcription factor-binding complexity.

DOI10.1093/narlgkx1251
Type of Journal (Indian or Foreign)Foreign
Impact Factor (IF)10.162
Divison category: 
Chemical Engineering & Process Development

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