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Iterative correction of Hi-C data reveals hallmarks of chromosome organization

Nature Methods volume 9, pages 999–1003 (2012)Cite this article

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Abstract

Extracting biologically meaningful information from chromosomal interactions obtained with genome-wide chromosome conformation capture (3C) analyses requires the elimination of systematic biases. We present a computational pipeline that integrates a strategy to map sequencing reads with a data-driven method for iterative correction of biases, yielding genome-wide maps of relative contact probabilities. We validate this ICE (iterative correction and eigenvector decomposition) technique on published data obtained by the high-throughput 3C method Hi-C, and we demonstrate that eigenvector decomposition of the obtained maps provides insights into local chromatin states, global patterns of chromosomal interactions, and the conserved organization of human and mouse chromosomes.

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Figure 1: Pipeline for mapping, filtering and iterative correction of Hi-C reads.
Figure 2: Iterative correction of Hi-C data.
Figure 3: Eigenvector decomposition of iteratively corrected Hi-C data reveals genome-wide features of chromosome organization.
Figure 4: Cross-data set and cross-species comparisons reveal evolutionary conserved genome-wide chromosome organization.

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Acknowledgements

The authors are grateful to K. Korolev for many productive discussions. The work of M.I., G.F., A.G. and L.M. were supported by the US National Cancer Institute Physical Sciences–Oncology Center at MIT (U54CA143874). This work was supported by US National Institutes of Health grants HG003143 (to J.D.) and F32GM100617 (to R.P.M.) and by a W.M. Keck Foundation Distinguished Young Scholar in Medical Research Award (to J.D.).

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Author notes

  1. Maxim Imakaev and Geoffrey Fudenberg: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Physics, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA

    Maxim Imakaev, Anton Goloborodko & Leonid A Mirny

  2. Graduate Program in Biophysics, Harvard University, Cambridge, Massachusetts, USA

    Geoffrey Fudenberg & Leonid A Mirny

  3. Department of Biochemistry and Molecular Pharmacology, Program in Systems Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Rachel Patton McCord, Natalia Naumova, Bryan R Lajoie & Job Dekker

  4. Institute for Medical Engineering and Science, MIT, Cambridge, Massachusetts, USA.,

    Leonid A Mirny

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  1. Maxim Imakaev
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  4. Natalia Naumova
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Contributions

M.I. developed the iterative correction procedure. M.I. and G.F. developed data analysis tools. M.I. and A.G. developed and maintain publicly available software. M.I., G.F., R.P.M. and A.G. performed data analysis. M.I., G.F., R.P.M., N.N., A.G., B.R.L., J.D. and L.A.M. contributed to conceiving the study and wrote the paper.

Corresponding authors

Correspondence to Job Dekker or Leonid A Mirny.

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The authors declare no competing financial interests.

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Supplementary Figures 1–16, Supplementary Table 1 and Supplementary Note (PDF 9595 kb)

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Imakaev, M., Fudenberg, G., McCord, R. et al. Iterative correction of Hi-C data reveals hallmarks of chromosome organization. Nat Methods 9, 999–1003 (2012). https://doi.org/10.1038/nmeth.2148

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