Identification of significant chromatin contacts from HiChIP data by FitHiChIP
Open accessPublished version of a preprint
Abstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Many computational algorithms for Hi-C analysis explicitly correct for distance decay, identifying significant interactions based on how unusual their contact frequency is at a given distance.
“many computational algorithms for the analysis of data from Hi-C and related techniques explicitly correct for distance decay, identifying “significant interactions” based on how unusual their contact frequency is at a given distance [277, 468–471].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [469]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 53 · Cited by 238
Research works printed but not linked: 32
- [1]Lieberman-Aiden E Comprehensive mapping of long-range interactions reveals folding principles of the human genome Science 2009 326 289 293 10.1126/science.1181369 19815776 PMC2858594 · DOI · Paper page
- [2]Duan Z A three-dimensional model of the yeast genome Nature 2010 465 363 367 10.1038/nature08973 20436457 PMC2874121 · DOI
- [3]Rao SS A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping Cell 2014 159 1665 1680 10.1016/j.cell.2014.11.021 25497547 PMC5635824 · DOI · Paper page
- [4]Fullwood MJ Ruan Y ChIP-based methods for the identification of long-range chromatin interactions J. Cell. Biochem. 2009 107 30 39 10.1002/jcb.22116 19247990 PMC2748757 · DOI
- [5]Mumbach MR HiChIP: efficient and sensitive analysis of protein-directed genome architecture Nat. Methods 2016 13 919 922 10.1038/nmeth.3999 27643841 PMC5501173 · DOI · Paper page
- [7]Ay F Bailey TL Noble WS Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts Genome Res. 2014 24 999 1011 10.1101/gr.160374.113 24501021 PMC4032863 · DOI
- [8]Mifsud B Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C Nat. Genet. 2015 47 598 606 10.1038/ng.3286 25938943 · DOI · Paper page
- [9]Carty M An integrated model for detecting significant chromatin interactions from high-resolution Hi-C data Nat. Commun. 2017 8 15454 10.1038/ncomms15454 28513628 PMC5442359 · DOI
- [10]Xu Z A hidden Markov random field-based Bayesian method for the detection of long-range chromosomal interactions in Hi-C data Bioinformatics 2016 32 650 656 10.1093/bioinformatics/btv650 26543175 PMC6280722 · DOI
- [11]Phanstiel DH Boyle AP Heidari N Snyder MP Mango: a bias-correcting ChIA-PET analysis pipeline Bioinformatics 2015 31 3092 3098 10.1093/bioinformatics/btv336 26034063 PMC4592333 · DOI
- [12]Paulsen J Rϕdland EA Holden L Holden M Hovig E A statistical model of ChIA-PET data for accurate detection of chromatin 3D interactions Nucleic Acids Res. 2014 42 e143 10.1093/nar/gku738 25114054 PMC4191384 · DOI
- [13]He C Zhang MQ Wang X MICC: an R package for identifying chromatin interactions from ChIA-PET data Bioinformatics 2015 31 3832 3834 26231426 PMC4653385
- [14]Lareau CA Aryee M J. hichipper: a preprocessing pipeline for calling DNA loops from HiChIP data Nat. Methods 2018 15 155 156 10.1038/nmeth.4583 29489746 PMC10572103 · DOI
- [15]Zhang Y Model-based analysis of ChIP-Seq (MACS) Genome Biol. 2008 9 R137 10.1186/gb-2008-9-9-r137 18798982 PMC2592715 · DOI · Paper page
- [17]Hu M HiCNorm: removing biases in Hi-C data via Poisson regression Bioinformatics 2012 28 3131 3133 10.1093/bioinformatics/bts570 23023982 PMC3509491 · DOI
- [18]Mumbach MR HiChIRP reveals RNA-associated chromosome conformation Nat. Methods 2019 16 489 492 10.1038/s41592-019-0407-x 31133759 PMC6638558 · DOI
- [20]Heidari N Genome-wide map of regulatory interactions in the human genome Genome Res. 2014 24 1905 1917 10.1101/gr.176586.114 25228660 PMC4248309 · DOI · Paper page
- [24]Gasperini M A genome-wide framework for mapping gene regulation via cellular genetic screens Cell 2019 176 1 14 10.1016/j.cell.2018.11.029 30612741 PMC6690346 · DOI · Paper page
- [26]Robinson MD McCarthy DJ Smyth GK edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Bioinformatics 2010 26 139 140 10.1093/bioinformatics/btp616 19910308 PMC2796818 · DOI · Paper page
- [27]McCarthy DJ Chen Y Smyth GK Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation Nucleic Acids Res. 2012 40 4288 4297 10.1093/nar/gks042 22287627 PMC3378882 · DOI · Paper page
- [28]Petrovic J Oncogenic notch promotes long-range regulatory interactions within hyperconnected 3D cliques Mol. Cell 2019 73 1174 1190 10.1016/j.molcel.2019.01.006 30745086 PMC6485942 · DOI
- [31]Dunham I Kundaje A Aldred SF al e An integrated encyclopedia of DNA elements in the human genome Nature 2012 489 57 74 10.1038/nature11247 22955616 PMC3439153 · DOI · Paper page
- [35]Trivedi KS Probability and Statistics with Reliability, Queuing and Computer Science Applications 2002 2nd edn Chichester, UK Wiley
- [36]West, D. B. Introduction to Graph Theory 2nd edn (Prentice Hall, Upper Saddle River, 2000).
- [37]Hagberg, A. A., Schult, D. A. & Swart, P. J. Exploring network structure, dynamics, and function using NetworkX. In Proc. 7th Python in Science Conference (SciPy2008), 11–15 (Pasadena, CA USA, 2008).
- [38]Ay F Noble WS Analysis methods for studying the 3D architecture of the genome Genome Biol. 2015 16 183 10.1186/s13059-015-0745-7 26328929 PMC4556012 · DOI
- [39]Dowen JM Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes Cell 2014 159 374 387 10.1016/j.cell.2014.09.030 25303531 PMC4197132 · DOI · Paper page
- [41]Langmead B Salzberg SL Fast gapped-read alignment with Bowtie 2 Nat. Methods 2012 9 357 359 10.1038/nmeth.1923 22388286 PMC3322381 · DOI · Paper page
- [43]Durand NC Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments Cell Syst. 2016 3 95 98 10.1016/j.cels.2016.07.002 27467249 PMC5846465 · DOI
- [44]Marshall AW Olkin I Scaling of matrices to achieve specified row and column sums Numer. Math. 1968 12 83 90 10.1007/BF02170999 · DOI
- [45]Rothblum UG Schneider H Scalings of matrices which have prespecified row sums and column sums via optimization Linear Algebra Appl. 1989 114-115 737 764 10.1016/0024-3795(89)90491-6 · DOI
- [46]Zhou X Exploring long-range genome interactions using the WashU Epigenome Browser Nat. Methods 2013 10 375 376 10.1038/nmeth.2440 23629413 PMC3820286 · DOI
- Authors
- Bhattacharyya, S., Chandra, V., Vijayanand, P., & Ay, F.
- Affiliations
- La Jolla Institute for Immunology (US)
- Corresponding author
- Ay, Ferhat
- Venue
- Nature Communications
- Published
- 2019-09-17
- Volume
- 10
- Issue
- 1
- Pages
- 4221-4221
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6748947
- OpenAlex
- W2973702082
- Cited by
- 238
- References
- 53
- Citations by year
- 2026: 30 · 2025: 30 · 2024: 61 · 2023: 39 · 2022: 28 · 2021: 32 · 2020: 12 · 2019: 6
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (R35-GM128938, R24-AI108564)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- HiChIP, enhancer-promoter interactions, regulatory elements
- MeSH terms
- Animals, Binding Sites, Chromatin, Enhancer Elements, Genetic, Promoter Regions, Genetic, Computational Biology, Genomics, Chromatin Immunoprecipitation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review