FIREcaller: Detecting frequently interacting regions from Hi-C data
Open accessPublished version of a preprint
Abstract
Hi-C experiments have been widely adopted to study chromatin spatial organization, which plays an essential role in genome function. We have recently identified frequently interacting regions (FIREs) and found that they are closely associated with cell-type-specific gene regulation. However, computational tools for detecting FIREs from Hi-C data are still lacking. In this work, we present FIREcaller, a stand-alone, user-friendly R package for detecting FIREs from Hi-C data. FIREcaller takes raw Hi-C contact matrices as input, performs within-sample and cross-sample normalization, and outputs continuous FIRE scores, dichotomous FIREs, and super-FIREs. Applying FIREcaller to Hi-C data from various human tissues, we demonstrate that FIREs and super-FIREs identified, in a tissue-specific manner, are closely related to gene regulation, are enriched for enhancer-promoter (E-P) interactions, tend to overlap with regions exhibiting epigenomic signatures of cis-regulatory roles, and aid the interpretation or GWAS variants. The FIREcaller package is implemented in R and freely available at https://yunliweb.its.unc.edu/FIREcaller.
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?
There are 3,966 FIREs in NeuN+ cells and 3,967 FIREs in NeuN− cells.
“We detected 3966 and 3967 FIREs in NeuN+ and NeuN− cells, respectively (Fig. 1a and Supplementary Data 1)24.”
From Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders (2021) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386 · see citing works
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212 · see citing works
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., et al. (2009) · Science · doi:10.1126/science.1181369 · Cited by 8,898 · see citing works
Bolstad, B. M., Irizarry, R. A., Åstrand, M., & Speed, T. P. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.2.185 · Cited by 8,185 · see citing works
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829 · see citing works
Self-citationIntegrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368 · cited 3× · see citing works
“Next, we evaluated the relationship between FIREs and histone modifications in cortex samples [26,37,41].”
BackgroundMethodSelf-citationcirclize implements and enhances circular visualization in R
Gu, Z., Gu, L., Eils, R., Schlesner, M., & Brors, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu393 · Cited by 4,290 · see citing works
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J., Lin, C. Y., Kagey, M. H., Rahl, P. B., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.035 · Cited by 4,143 · see citing works
The ENCODE Blacklist: Identification of Problematic Regions of the Genome
Amemiya, H. M., Kundaje, A., & Boyle, A. P. (2019) · Scientific Reports · doi:10.1038/s41598-019-45839-z · Cited by 1,831 · see citing works
Common variants conferring risk of schizophrenia
†Genetic Risk and Outcome in Psychosis (GROUP), Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Cichon, S., Rujescu, D., Werge, T., Pietiläinen, O. P. H., Mors, O., et al. (2009) · Nature · doi:10.1038/nature08186 · Cited by 1,677 · see citing works
A high-resolution map of the three-dimensional chromatin interactome in human cells
Jin, F., Li, Y., Dixon, J. R., Selvaraj, S., Ye, Z., Lee, A. Y., Yen, C.-A., Schmitt, A. D., Espinoza, C. A., & Ren, B. (2013) · Nature · doi:10.1038/nature12644 · Cited by 1,208 · see citing works
Self-citationExploring the three-dimensional organization of genomes: Interpreting chromatin interaction data
Dekker, J., Marti-Renom, M. A., & Mirny, L. A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3454 · Cited by 1,068 · see citing works
Comprehensive functional genomic resource and integrative model for the human brain
Wang, D., Liu, S., Warrell, J., Won, H., Shi, X., Navarro, F. C. P., Clarke, D., Gu, M., Emani, P., Yang, Y. T., et al. (2018) · Science · doi:10.1126/science.aat8464 · Cited by 965 · see citing works
Self-citationA compendium of chromatin contact maps reveals spatially active regions in the human genome
Schmitt, A. D., Hu, M., Jung, I., Xu, Z., Qiu, Y., Tan, C. L., Li, Y., Lin, S., Lin, Y., Barr, C. L., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.061 · Cited by 866 · see citing works
Self-citationChromatin Domains: The Unit of Chromosome Organization
Dixon, J. R., Gorkin, D. U., & Ren, B. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.018 · Cited by 811 · see citing works
Self-citationIntegrative functional genomic analysis of human brain development and neuropsychiatric risks
Li, M., Santpere, G., Imamura Kawasawa, Y., Evgrafov, O. V., Gulden, F. O., Pochareddy, S., Sunkin, S. M., Li, Z., Shin, Y., Zhu, Y., et al. (2018) · Science · doi:10.1126/science.aat7615 · Cited by 810 · see citing works
Self-citationYaffe, E., & Tanay, A. (2011) · Nature Genetics · doi:10.1038/ng.947 · Cited by 645 · see citing works
Systematic mapping of functional enhancer–promoter connections with CRISPR interference
Fulco, C. P., Munschauer, M., Anyoha, R., Munson, G., Grossman, S. R., Perez, E. M., Kane, M., Cleary, B., Lander, E. S., & Engreitz, J. M. (2016) · Science · doi:10.1126/science.aag2445 · Cited by 643 · see citing works
Chromosome conformation elucidates regulatory relationships in developing human brain
Won, H., de la Torre-Ubieta, L., Stein, J. L., Parikshak, N. N., Huang, J., Opland, C. K., Gandal, M. J., Sutton, G. J., Hormozdiari, F., Lu, D., et al. (2016) · Nature · doi:10.1038/nature19847 · Cited by 584 · see citing works
Self-citationStatistical confidence estimation for Hi-C data reveals regulatory chromatin contactsPreprint
Ay, F., Bailey, T. L., & Noble, W. S. (2014) · Genome Research · doi:10.1101/gr.160374.113 · Cited by 479 · see citing works
The Hitchhiker's Guide to Hi-C Analysis: Practical guidelines
Lajoie, B., Dekker, J., & Kaplan, N. (2014) · Methods · doi:10.1016/j.ymeth.2014.10.031 · Cited by 367 · see citing works
The Three-Dimensional Organization of Mammalian Genomes
Yu, M., & Ren, B. (2017) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100616-060531 · Cited by 366 · see citing works
Self-citationA compendium of promoter-centered long-range chromatin interactions in the human genome
Jung, I., Schmitt, A., Diao, Y., Lee, A. J., Liu, T., Yang, D., Tan, C., Eom, J., Chan, M., Chee, S., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0494-8 · Cited by 362 · see citing works
Self-citationGenome-wide mapping and analysis of chromosome architecture
Schmitt, A. D., Hu, M., & Ren, B. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.104 · Cited by 344 · see citing works
Self-citationRegulation of disease-associated gene expression in the 3D genome
Krijger, P. H. L., & de Laat, W. L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.138 · Cited by 316 · see citing works
HiCNorm: removing biases in Hi-C data via Poisson regression
Hu, M., Deng, K., Selvaraj, S., Qin, Z., Ren, B., & Liu, J. S. (2012) · Bioinform. · doi:10.1093/bioinformatics/bts570 · Cited by 250 · see citing works
Self-citationIdentifying statistically significant chromatin contacts from Hi-C data with FitHiC2
Kaul, A., Bhattacharyya, S., & Ay, F. (2020) · Nature Protocols · doi:10.1038/s41596-019-0273-0 · Cited by 226 · see citing works
Population-based 3D genome structure analysis reveals driving forces in spatial genome organization
Tjong, H., Li, W., Kalhor, R., Dai, C., Hao, S., Gong, K. Q., Zhou, Y., Li, H., Zhou, X. J., Gros, M. A. L., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512577113 · Cited by 177 · see citing works
Song, M., Yang, X.-Y., Ren, X.-J., Maliskova, L., Li, B.-K., Jones, I. R., Wang, C., Jacob, F., Wu, K. Y., Traglia, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0472-1 · Cited by 172 · see citing works
Self-citationThe emerging roles of TCF4 in disease and development
Forrest, M. P., Hill, M., Quantock, A. J., Martin‐Rendon, E., & Blake, D. J. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.01.010 · Cited by 171 · see citing works
Measuring the reproducibility and quality of Hi-C data
Yardımcı, G. G., Özadam, H., Sauria, M. E. G., Ursu, O., Yan, K., Yang, T., Chakraborty, A., Kaul, A., Lajoie, B. R., Song, F., et al. (2019) · Genome biology · doi:10.1186/s13059-019-1658-7 · Cited by 171 · see citing works
Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders
Hu, B., Won, H., Mah, W., Park, R. B., Kassim, B., Spiess, K., Kozlenkov, A., Crowley, C. A., Pochareddy, S., The PsychENCODE Consortium, et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24243-0 · Cited by 103 · see citing works
Self-citationCommon DNA sequence variation influences 3-dimensional conformation of the human genome
Gorkin, D. U., Qiu, Y., Hu, M., Fletez‐Brant, K., Liu, T., Schmitt, A. D., Noor, A., Chiou, J., Gaulton, K. J., Sebat, J. L., et al. (2019) · Genome biology · doi:10.1186/s13059-019-1855-4 · Cited by 81 · see citing works
Self-citationHalvorsen, M., Huh, R., Oskolkov, N., Wen, J., Netotea, S., Giusti‐Rodríguez, P., Karlsson, R., Bryois, J., Nystedt, B., Ameur, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15707-w · Cited by 81 · see citing works
Self-citationTADCompare: An R Package for Differential and Temporal Analysis of Topologically Associated Domains
Cresswell, K. G., & Dozmorov, M. G. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00158 · Cited by 80 · see citing works
Giusti‐Rodríguez, P., & Sullivan, P. F. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/406330 · Cited by 72 · see citing works
Gene regulation in the 3D genome
Li, Y., Hu, M., & Shen, Y. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy164 · Cited by 66 · see citing works
Self-citationHUGIn: Hi-C Unifying Genomic Interrogator
Martin, J. S., Xu, Z. Q., Reiner, A. P., Mohlke, K. L., Sullivan, P. F., Ren, B., Hu, M., & Li, Y. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx359 · Cited by 61 · see citing works
Self-citationXu, Z. Q., Zhang, G., Jin, F., Chen, M., Furey, T. S., Sullivan, P. F., Qin, Z. S., Hu, M., & Li, Y. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv650 · Cited by 48 · see citing works
Self-citationFastHiC: a fast and accurate algorithm to detect long-range chromosomal interactions from Hi-C data
Xu, Z. Q., Zhang, G., Wu, C., Li, Y., & Hu, M. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw240 · Cited by 37 · see citing works
Self-citationNeuronal and glial 3D chromatin architecture illustrates cellular etiology of brain disordersPreprint
Hu, B., Won, H., Mah, W., Park, R., Kassim, B. S., Spiess, K., Kozlenkov, A., Crowley, C., Pochareddy, S., Li, Y., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.14.096917 · Cited by 11 · see citing works
Self-citationDeciphering non-coding variation with 3D epigenomics
Burgess, D. J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.161 · Cited by 7 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [13]Rao S.P. A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping Cell 159 7 2014 1665 1680 10.1016/j.cell.2014.11.021 25497547 PMC5635824 · DOI · Paper page
Cited by
Sorted by citations
Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
Einkauf, K. B., Osborn, M. R., Gao, C., Sun, W., Sun, X., Lian, X., Parsons, E. M., Gladkov, G. T., Seiger, K. W., Blackmer, J. E., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.011 · Cited by 260 · see citing works
Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders
Hu, B., Won, H., Mah, W., Park, R. B., Kassim, B., Spiess, K., Kozlenkov, A., Crowley, C. A., Pochareddy, S., The PsychENCODE Consortium, et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24243-0 · Cited by 103 · see citing works
Self-citation
- Authors
- Crowley, C., Yang, Y., Qiu, Y., Hu, B., Abnousi, A., Lipiński, J., Plewczyński, D., Wu, D., Won, H., Ren, B., Hu, M., & Li, Y.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of California San Diego (US)
- Cleveland Clinic (US)
- Cellular Genomics, Warsaw, Poland
- Warsaw University of Technology (PL)
- Corresponding author
- Yang, Yuchen
- Hu, Ming
- Li, Yun
- ORCID
- Venue
- Computational and Structural Biotechnology Journal
- Published
- 2020-12-31
- Volume
- 19
- Pages
- 355-362
- ISSN
- 2001-0370 (ISSN-L)
- PMC
- PMC7788093
- OpenAlex
- W3117820463
- Cited by
- 37
- References
- 42
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2022: 9 · 2021: 13
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Computational and Structural Biotechnology Journal (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of North Carolina at Chapel Hill
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromatin spatial organization, enhancer-promoter interactions, cell type-specific gene regulation, cis-regulatory elements, R package
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