HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis

Abstract

We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco11. In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, http://molotool.autosome.ru) that applies HOCOMOCO models for visualization of binding sites in short DNA sequences.

Integration of multiple epigenomic marks improves prediction of variant impact in saturation mutagenesis reporter assay

“…Conservation scores were generated from phyloP100way, phastCons100way, and MultiZ alignments. Dinucleotide PWMs from HOCOMOCO (Kulakovskiy et al, ) were used for the motif analysis. SPRY‐SARUS and PERFECTOS‐APE (Vorontsov, Kulakovskiy, Khimulya, Nikolaeva, & Makeev, ) were used to map motif occurrences within reporter regions and to assess the difference of motif P‐values for alternative alleles.…”

Molecular and Functional Sex Differences of Noradrenergic Neurons in the Mouse Locus Coeruleus

“…Masked flanking sequences were submitted to MEME (Bailey et al, 2015) for de novo discovery of motifs 8–20 bp long. The associated tool, TomTom, was used to compare motifs to known transcription factor (TF) binding sites (Kulakovskiy et al, 2018; Mathelier et al, 2016; Weirauch et al, 2014). Motif frequency, consensus sequence, and predicted TFs discussed in the text are provided (Table S2).…”

PWMScan: a fast tool for scanning entire genomes with a position-specific weight matrix

“…By summing up weights at corresponding positions, a binding score can be computed for any base sequence of the same length as the PWM. Large collections of TF specificity matrices are nowadays available from public libraries such as JASPAR (Khan et al , 2017) or HOCOMOCO (Kulakovskiy et al , 2017). …”