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Statistical Shape Theory and Registration Methods for Analyzing the 3D Architecture of Chromatin in Interphase Cell Nuclei

  • Siwei Yang
  • Doris Illner
  • Kathrin Teller
  • Irina Solovei
  • Roel van Driel
  • Boris Joffe
  • Thomas Cremer
  • Roland Eils
  • Karl Rohr
Chapter

Abstract

For studying the 3D structure formed by consecutive genomic regions of chromosomes we propose using statistical shape theory in conjunction with registration methods. In contrast to earlier work, where the 3D chromatin structure was analyzed indirectly, we here directly exploit the 3D locations of genomic regions to determine the large-scale structure of chromatin fiber. Our study is based on 3D microscopy images of the X-chromosome where four consecutive genomic regions (BACs) have been simultaneously labeled by multicolor FISH. To allow unique reconstruction of the 3D shape, image data with sets of four consecutive BACs have been acquired with an overlap of three BACs between the different sets. We have statistically analyzed the data and it turned out that for all datasets the 3D structure is non-random. In addition, we found that the shapes of active and inactive X-chromosomal genomic regions are statistically independent. Moreover, we reconstructed the 3D structure of chromatin in a small genomic region based on five BACs resulting from two overlapping four BACs. We also found that spatial normalization of cell nuclei using non-rigid image registration has a significant influence on the location of the genomic regions.

Keywords

Bacterial Artificial Chromosome Registration Method Concentration Parameter Shape Space Chromosome Territory 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work has been supported by the EU project 3DGENOME. TC also acknowledges the support by the Wilhelm-Sanderstiftung (2001.079.2). The work benefited from the use of the Insight Toolkit (ITK) Ibanez et al. (2005) and the Visualization Toolkit (VTK) (Schroeder et al. 2003).

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Copyright information

© Springer Netherlands 2011

Authors and Affiliations

  • Siwei Yang
    • 1
  • Doris Illner
    • 2
  • Kathrin Teller
    • 2
  • Irina Solovei
    • 2
  • Roel van Driel
    • 3
  • Boris Joffe
    • 2
  • Thomas Cremer
    • 2
  • Roland Eils
    • 1
  • Karl Rohr
    • 1
  1. 1.Department of Bioinformatics and Functional Genomics, Biomedical Computer Vision Group (BMCV)University of Heidelberg, BioQuant Center, IPMB, and German Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Department of Biology II, Anthropology and Human GeneticsLudwig Maximilians University MunichBiozentrumGermany
  3. 3.Research group: Structural and Functional Organization of the Cell Nucleus, Swammerdam Institute for Life Sciences (SILS)University of Amsterdam, BioCentrum AmsterdamAmsterdamThe Netherlands

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