Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 17;18(8):e0289651.
doi: 10.1371/journal.pone.0289651. eCollection 2023.

Multidimensional scaling methods can reconstruct genomic DNA loops using Hi-C data properties

Ryo Ishibashi  1
Affiliations

Multidimensional scaling methods can reconstruct genomic DNA loops using Hi-C data properties

Ryo Ishibashi. PLoS One. .

Abstract

This paper proposes multidimensional scaling (MDS) applied to high-throughput chromosome conformation capture (Hi-C) data on genomic interactions to visualize DNA loops. Currently, the mechanisms underlying the regulation of gene expression are poorly understood, and where and when DNA loops are formed remains undetermined. Previous studies have focused on reproducing the entire three-dimensional structure of chromatin; however, identifying DNA loops using these data is time-consuming and difficult. MDS is an unsupervised method for reconstructing the original coordinates from a distance matrix. Here, MDS was applied to high-throughput chromosome conformation capture (Hi-C) data on genomic interactions to visualize DNA loops. Hi-C data were converted to distances by taking the inverse to reproduce loops via MDS, and the missing values were set to zero. Using the converted data, MDS was applied to the log-transformed genomic coordinate distances and this process successfully reproduced the DNA loops in the given structure. Consequently, the reconstructed DNA loops revealed significantly more DNA-transcription factor interactions involved in DNA loop formation than those obtained from previously applied methods. Furthermore, the reconstructed DNA loops were significantly consistent with chromatin immunoprecipitation followed by sequencing (ChIP-seq) peak positions. In conclusion, the proposed method is an improvement over previous methods for identifying DNA loops.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The flowchart of analyses performed in this study.
Fig 2
Fig 2. Plot of the distance between coordinates versus the natural logarithm of Hi-C contact frequency before multiplying by weight 0–50,000 kbp of chromosome 5 by series GSM6061774.
Fig 3
Fig 3. Plot of the distance between coordinates versus the natural logarithm of Hi-C contact frequency after multiplying by weight 0–50,000 kbp of chromosome 5 by series GSM6061774.
Fig 4
Fig 4. Plot of the second and third eigenvectors.
Chromosome 5 0–50,000 kbp by series GSM6061774 after MDS. The blue line represents the root of the DNA loop, which is defined in Section 2.2.4.
Fig 5
Fig 5. Distance plot between coordinates of chromosome 5 0–50,000 kbp by series GSM6061774.
The red line is the threshold, and the blue points are the roots of the DNA loop, which is defined in Section 2.2.4.
Fig 6
Fig 6. Distance plot between coordinates of chromosome 5 50,000–100,000 kbp of series GSM6061774 by the MDS-based method.
Fig 7
Fig 7. Distance plot between coordinates of chromosome 5 50,000–100,000 kbp of series GSM6061774 by the previous MDS-based method.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Matthews K. DNA looping. Microbiological reviews. 1992;56(1):123–136. doi: 10.1128/mr.56.1.123-136.1992 - DOI - PMC - PubMed
    1. Nagano T, Lubling Y, Stevens TJ, Schoenfelder S, Yaffe E, Dean W, et al.. Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature. 2013;502(7469):59–64. doi: 10.1038/nature12593 - DOI - PMC - PubMed
    1. Lieberman-Aiden E, Van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, et al.. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. science. 2009;326(5950):289–293. doi: 10.1126/science.1181369 - DOI - PMC - PubMed
    1. Kloetgen A, Thandapani P, Ntziachristos P, Ghebrechristos Y, Nomikou S, Lazaris C, et al.. Three-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia. Nature genetics. 2020;52(4):388–400. doi: 10.1038/s41588-020-0602-9 - DOI - PMC - PubMed
    1. Díaz N, Kruse K, Erdmann T, Staiger AM, Ott G, Lenz G, et al.. Chromatin conformation analysis of primary patient tissue using a low input Hi-C method. Nature communications. 2018;9(1):1–13. doi: 10.1038/s41467-018-06961-0 - DOI - PMC - PubMed