Clique-Based Topological Characterization of Chromatin Interaction Hubs

  • Conference paper
  • First Online:
Bioinformatics Research and Applications (ISBRA 2023)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 14248))

Included in the following conference series:

Abstract

Chromatin conformation capture technologies are a vital source of information about the spatial organization of chromatin in eukaryotic cells. Of these technologies, Hi-C and related methods have been widely used to obtain reasonably complete contact maps in many cell lines and tissues under a wide variety of conditions. This data allows for the creation of chromatin interaction graphs from which topological generalizations about the structure of chromatin may be drawn. Here we outline and utilize a clique-based approach to analyzing chromatin interaction graphs which allows for both detailed analysis of strongly interconnected regions of chromatin and the unraveling of complex relationships between genomic loci in these regions. We find that clique-rich regions are significantly enriched in distinct gene ontologies as well as regions of transcriptional activity compared to the entire set of links in the respective datasets, and that these cliques are also not entirely preserved in randomized Hi-C data. We conclude that cliques and the denser regions of connectivity in which they are common appear to indicate a consistent pattern of chromatin spatial organization that resembles transcription factories, and that cliques can be used to identify functional modules in Hi-C data.

Supported by the Latvian Council of Science project lzp-2021/1-0236.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Adams, D., Altucci, L., et al.: BLUEPRINT to decode the epigenetic signature written in blood. Nat. Biotechnol. 30(3), 224–226 (2012). https://doi.org/10.1038/nbt.2153

    Article  CAS  PubMed  Google Scholar 

  2. Ashburner, M., Ball, C.A., et al.: Gene Ontology: tool for the unification of biology. Nat. Genet. 25(1), 25–29 (2000). https://doi.org/10.1038/75556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cairns, J., Freire-Pritchett, P., et al.: CHiCAGO: robust detection of DNA loo** interactions in Capture Hi-C data. Genome Biol. 17(1), 127 (2016). https://doi.org/10.1186/s13059-016-0992-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Collas, P., Liyakat Ali, T.M., et al.: Finding friends in the crowd: three-dimensional cliques of topological genomic domains. Front. Genet. 10, 602 (2019). https://doi.org/10.3389/fgene.2019.00602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cunningham, F., Allen, J.E., et al.: Ensembl 2022. Nucleic Acids Res. 50(D1), D988–D995 (2022). https://doi.org/10.1093/nar/gkab1049

  6. Grubert, F., Srivas, R., et al.: Landscape of cohesin-mediated chromatin loops in the human genome. Nature 583(7818), 737–743 (2020). https://doi.org/10.1038/s41586-020-2151-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Javierre, B.M., Sewitz, S., et al.: Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters. Cell 167(5), 1369–1384.e19 (2016). https://doi.org/10.1016/j.cell.2016.09.037

  8. Jha, R.K., Levens, D., Kouzine, F.: Mechanical determinants of chromatin topology and gene expression. Nucleus 13(1), 95–116 (2022). https://doi.org/10.1080/19491034.2022.2038868

    Article  CAS  Google Scholar 

  9. Jung, I., Schmitt, A., et al.: A compendium of promoter-centered long-range chromatin interactions in the human genome. Nat. Genet. 51(10), 1442–1449 (2019). https://doi.org/10.1038/s41588-019-0494-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kim, K., Jang, I., et al.: 3DIV update for 2021: a comprehensive resource of 3D genome and 3D cancer genome. Nucleic Acids Res. 49(D1), D38–D46 (2021). https://doi.org/10.1093/nar/gkaa1078

    Article  CAS  PubMed  Google Scholar 

  11. Klopfenstein, D.V., Zhang, L., et al.: GOATOOLS: a python library for gene ontology analyses. Sci. Rep. 8(1), 10872 (2018). https://doi.org/10.1038/s41598-018-28948-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kundaje, A., Meuleman, W., et al.: Integrative analysis of 111 reference human epigenomes. Nature 518(7539), 317–330 (2015). https://doi.org/10.1038/nature14248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lieberman-Aiden, E., Van Berkum, N.L., et al.: Comprehensive map** of long-range interactions reveals folding principles of the human genome. Science 326(5950), 289–293 (2009). https://doi.org/10.1126/science.1181369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu, L., Li, Q.Z., et al.: Revealing gene function and transcription relationship by reconstructing gene-level chromatin interaction. Comput. Struct. Biotechnol. J. 17, 195–205 (2019). https://doi.org/10.1016/j.csbj.2019.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liyakat Ali, T.M., Brunet, A., et al.: TAD cliques predict key features of chromatin organization. BMC Genom. 22(1), 499 (2021). https://doi.org/10.1186/s12864-021-07815-8

    Article  CAS  Google Scholar 

  16. Lohia, R., Fox, N., Gillis, J.: A global high-density chromatin interaction network reveals functional long-range and trans-chromosomal relationships. Genome Biol. 23(1), 238 (2022). https://doi.org/10.1186/s13059-022-02790-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Maeshima, K., Tamura, S., et al.: Fluid-like chromatin: toward understanding the real chromatin organization present in the cell. Curr. Opin. Cell Biol. 64, 77–89 (2020). https://doi.org/10.1016/j.ceb.2020.02.016

    Article  CAS  PubMed  Google Scholar 

  18. Mora, A., Huang, X., et al.: Chromatin hubs: a biological and computational outlook. Comput. Struct. Biotechnol. J. 20, 3796–3813 (2022). https://doi.org/10.1016/j.csbj.2022.07.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pancaldi, V.: Network models of chromatin structure. Curr. Opin. Genet. Dev. 80, 102051 (2023). https://doi.org/10.1016/j.gde.2023.102051

    Article  CAS  PubMed  Google Scholar 

  20. Sanalkumar, R., Dong, R., et al.: Highly connected 3D chromatin networks established by an oncogenic fusion protein shape tumor cell identity. Sci. Adv. 9(13) (2023). https://doi.org/10.1126/sciadv.abo3789

  21. Sandhu, K.S., Li, G., et al.: Large-scale functional organization of long-range chromatin interaction networks. Cell Rep. 2(5), 1207–1219 (2012). https://doi.org/10.1016/j.celrep.2012.09.022

  22. Sutherland, H., Bickmore, W.A.: Transcription factories: gene expression in unions? Nat. Rev. Genet. 10(7), 457–466 (2009). https://doi.org/10.1038/nrg2592

    Article  CAS  PubMed  Google Scholar 

  23. Szabo, Q., Bantignies, F., Cavalli, G.: Principles of genome folding into topologically associating domains. Sci. Adv. 5(4) (2019). https://doi.org/10.1126/sciadv.aaw1668

  24. Tao, H., Li, H., et al.: Computational methods for the prediction of chromatin interaction and organization using sequence and epigenomic profiles. Brief. Bioinf. (2021). https://doi.org/10.1093/bib/bbaa405

    Article  Google Scholar 

  25. Volpi, E., Chevret, E., et al.: Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei. J. Cell Sci. 113(9), 1565–1576 (2000). https://doi.org/10.1242/jcs.113.9.1565

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gatis Melkus .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Melkus, G. et al. (2023). Clique-Based Topological Characterization of Chromatin Interaction Hubs. In: Guo, X., Mangul, S., Patterson, M., Zelikovsky, A. (eds) Bioinformatics Research and Applications. ISBRA 2023. Lecture Notes in Computer Science(), vol 14248. Springer, Singapore. https://doi.org/10.1007/978-981-99-7074-2_38

Download citation

  • DOI: https://doi.org/10.1007/978-981-99-7074-2_38

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-99-7073-5

  • Online ISBN: 978-981-99-7074-2

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics

Navigation