FourCSeq: Analysis of 4C sequencing data

BioRxiv : the Preprint Server for Biology
Felix A. KleinWolfgang Huber

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 transformed 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 statistical method DESeq2 adapted from RNA-Seq analysis. Availability and Implementation A full end-to-end analysis pipeline is implemented in the R package FourC...Continue Reading

Related Concepts

Genome
Ligation
Motivation
Spatial Distribution
Sequence Analysis, RNA
Analysis
Genomic Stability
Nucleic Acid Sequencing
probe gene fragment
Computer Program Package

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