Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs

Chromatin looping is an essential feature of eukaryotic genomes and can bring regulatory sequences, such as enhancers or transcription factor binding sites, in the close physical proximity of regulated target genes. Here, we provide sevenC, an R package that uses protein binding signals from ChIP-seq and sequence motif information to predict chromatin looping events. Cross-linking of proteins that bind close to loop anchors result in ChIP-seq signals at both anchor loci. These signals are used at CTCF motif pairs together with their distance and orientation to each other to predict whether they interact or not. The resulting chromatin loops might be used to associate enhancers or transcription factor binding sites (e.g., ChIP-seq peaks) to regulated target genes.

A more detailed explanation of the sevenC method together with prediction performance analysis is available in the associated preprint:

Ibn-Salem, J. & Andrade-Navarro, M. A. Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs. bioRxiv 257584 (2018). https://doi.org/10.1101/257584

Intallation

To install the sevenC package, start R and enter:

if (!requireNamespace("BiocManager", quietly=TRUE))
    install.packages("BiocManager")
BiocManager::install("sevenC")

Alternatively, the development version of sevenC can be installed from GitHub:

#install.packages("devtools")
devtools::install_github("ibn-salem/sevenC")

Basic usage example

Here we show how to use sevenC to predict chromatin looping interactions among CTCF motif locations on chromosome 22. As input, we only use CTCF motif locations and a single bigWig file from a STAT1 ChIP-seq experiment in human GM12878 cells.

Get motif pairs

library(sevenC)

# load provided CTCF motifs in human genome
motifs <- motif.hg19.CTCF.chr22

# get motifs pairs
gi <- prepareCisPairs(motifs, maxDist = 10^6)

Add ChIP-seq data and compute correaltion

# use example ChIP-seq bigWig file
bigWigFile <- system.file("extdata", "GM12878_Stat1.chr22_1-30000000.bigWig", 
  package = "sevenC")

# add ChIP-seq coverage and compute correaltion at motif pairs
gi <- addCor(gi, bigWigFile)

Predict loops

# predict looping interactions among all motif pairs
loops <- predLoops(gi)

For more detailed usage instructions, see the package vignette or reference documentation.

Issues

Please report issues here: https://github.com/ibn-salem/sevenC/issues

sevenC