Increased peak detection accuracy in over-dispersed ChIP-seq data with supervised segmentation models

Arnaud Liehrmann, Guillem Rigaill, Toby Dylan Hocking

Research output: Contribution to journalArticlepeer-review


Background: Histone modification constitutes a basic mechanism for the genetic regulation of gene expression. In early 2000s, a powerful technique has emerged that couples chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq). This technique provides a direct survey of the DNA regions associated to these modifications. In order to realize the full potential of this technique, increasingly sophisticated statistical algorithms have been developed or adapted to analyze the massive amount of data it generates. Many of these algorithms were built around natural assumptions such as the Poisson distribution to model the noise in the count data. In this work we start from these natural assumptions and show that it is possible to improve upon them. Results: Our comparisons on seven reference datasets of histone modifications (H3K36me3 & H3K4me3) suggest that natural assumptions are not always realistic under application conditions. We show that the unconstrained multiple changepoint detection model with alternative noise assumptions and supervised learning of the penalty parameter reduces the over-dispersion exhibited by count data. These models, implemented in the R package CROCS (, detect the peaks more accurately than algorithms which rely on natural assumptions. Conclusion: The segmentation models we propose can benefit researchers in the field of epigenetics by providing new high-quality peak prediction tracks for H3K36me3 and H3K4me3 histone modifications.

Original languageEnglish (US)
Article number323
JournalBMC Bioinformatics
Issue number1
StatePublished - Dec 2021


  • ChIP-seq
  • Histone modifications
  • Likelihood inference
  • Multiple changepoint detection
  • Over-dispersion
  • Peak calling
  • Supervised learning

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics


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