title: FourCSeq: analysis of 4C sequencing data.
abstract: BACKGROUND
  Circularized Chromosome Conformation Capture (4C) is a powerful technique for studying the spatial interactions of a specific genomic region called the 'viewpoint' with the rest of the genome, both in a single condition or comparing different experimental conditions or cell types. Observed ligation frequencies typically 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 peaks and to detect changes between different biological conditions.
  
  
  RESULTS
  We model the overall trend of decreasing interaction frequency with genomic distance by fitting a smooth monotonically decreasing function to suitably transformed count data. Based on the fit, z-scores are calculated from the residuals, and high z-scores are 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.
  
  
  METHODS
  A full end-to-end analysis pipeline is implemented in the R package FourCSeq available at www.bioconductor.org.
  
  
  BACKGROUND
  felix.klein@embl.de or whuber@embl.de
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors.forename: Felix A
authors.initials: FA
authors.lastname: Klein
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors.forename: Tibor
authors.initials: T
authors.lastname: Pakozdi
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Anders
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors.forename: Yad
authors.initials: Y
authors.lastname: Ghavi-Helm
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors.forename: Eileen E M
authors.initials: EE
authors.lastname: Furlong
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huber
mesh_terms: D002875:Chromosomes / Q000235:genetics*; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D009690:Nucleic Acid Conformation; D013223:Statistics as Topic