Identification of significant chromatin contacts from HiChIP data by FitHiChIP

Nat Commun. 2019 Sep 17;10(1):4221. doi: 10.1038/s41467-019-11950-y.


HiChIP/PLAC-seq is increasingly becoming popular for profiling 3D chromatin contacts among regulatory elements and for annotating functions of genetic variants. Here we describe FitHiChIP, a computational method for loop calling from HiChIP/PLAC-seq data, which jointly models the non-uniform coverage and genomic distance scaling of contact counts to compute statistical significance estimates. We also develop a technique to filter putative bystander loops that can be explained by stronger adjacent loops. Compared to existing methods, FitHiChIP performs better in recovering contacts reported by Hi-C, promoter capture Hi-C and ChIA-PET experiments and in capturing previously validated promoter-enhancer interactions. FitHiChIP loop calls are reproducible among replicates and are consistent across different experimental settings. Our work also provides a framework for differential HiChIP analysis with an option to utilize ChIP-seq data for further characterizing differential loops. Even though designed for HiChIP, FitHiChIP is also applicable to other conformation capture assays.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Chromatin / chemistry*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation / methods*
  • Computational Biology / methods*
  • Enhancer Elements, Genetic
  • Genomics
  • Mice
  • Promoter Regions, Genetic


  • Chromatin