FourCSeq: Analysis of 4C sequencing data

Abstract Motivation: Circularized Chromosome Conformation Capture (4C) is a powerful technique for studying the spatial interactions of a specific genomic region called the “view- point” with the rest of the genome, both in a single condition or comparing different experimental conditions or cell types. Observed ligation frequencies show a strong, regular dependence on genomic distance from the viewpoint, on top of which specific interaction peaks are superimposed. Here, we address the computational task to find these specific interactions and to detect changes between interaction profiles of different conditions. Results: We model the overall trend of decreasing interaction frequency with genomic distance by fitting a smooth monotonously decreasing function to suitably trans- formed count data. Based on the fit, z-scores are calculated from the residuals, with high z scores being interpreted as peaks providing evidence for specific interactions. To compare different conditions, we normalize fragment counts between samples, and call for differential contact frequencies using the statisti- cal method DESeq2 adapted from RNA-Seq analysis. Availability and Implementation: A full end-to-end analysis pipeline is implemented in the R package FourCSeq available at http://www.bioconductor.orgwww.bioconductor.org.