Abstract
Recent chromosome conformation capture experiments have led to the discovery of dense, contiguous, megabase-sized topological domains that are similar across cell types, are conserved across species. These domains are strongly correlated with a number of chromatin markers and have since been included in a number of analyses. However, functionally relevant domains may exist at multiple length scales. We introduce a new and efficient algorithm that is able to capture persistent domains across various resolutions by adjusting a single scale parameter. The identified novel domains are substantially different from domains reported previously and are highly enriched for insulating factor CTCF binding and histone modifications at the boundaries.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bickmore, W.A., van Steensel, B.: Genome Architecture: domain organization of interphase chromosomes. Cell 152(6), 1270–1284 (2013)
Cavalli, G., Misteli, T.: Functional implications of genome topology. Nature Structural & Molecular Biology 20(3), 290–299 (2013)
de Wit, E., de Laat, W.: A decade of 3C technologies: insights into nuclear organization.. Genes & Development 26(1), 11–24 (2012)
Dixon, J.R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J.S., Ren, B.: Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485(7398), 376–380 (2012)
Filippova, D., Gadani, A., Kingsford, C.: Coral: an integrated suite of visualizations for comparing clusterings. BMC Bioinformatics 13(1), 276 (2012)
Fudenberg, G., Getz, G., Meyerson, M., Mirny, L.A.: High order chromatin architecture shapes the landscape of chromosomal alterations in cancer. Nature Biotechnology 29(12), 1109–1113 (2011)
Gibcus, J.H., Dekker, J.: The hierarchy of the 3D genome. Molecular Cell 49(5), 773–782 (2013)
Goldberg, A.V.: Finding a maximum density subgraph. Computer Science Division. University of California, Berkeley (1984)
Hou, C., Li, L., Qin, Z.S., Corces, V.G.: Gene density, transcription, and insulators contribute to the partition of the Drosophila genome into physical domains. Molecular cell 48(3), 471–484 (2012)
Kim, T.H., Abdullaev, Z.K., Smith, A.D., Ching, K.A., Loukinov, D.I., Green, R.D., Zhang, M.Q., Lobanenkov, V.V., Ren, B.: Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell 128(6), 1231–1245 (2007)
Kleinberg, J., Tardos, É.: Algorithm Design. Addison-Wesley, Boston (2005)
Kölbl, A.C., Weigl, D., Mulaw, M., Thormeyer, T., Bohlander, S.K., Cremer, T., Dietzel, S.: The radial nuclear positioning of genes correlates with features of megabase-sized chromatin domains.. Chromosome Research 20(6), 735–752 (2012)
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.: Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326(5950), 289–293 (2009)
Lin, Y.C., Benner, C., Mansson, R., Heinz, S., Miyazaki, K., Miyazaki, M., Chandra, V., Bossen, C., Glass, C.K., Murre, C.: Global changes in the nuclear positioning of genes and intra- and interdomain genomic interactions that orchestrate B cell fate. Nature Immunology 13(12), 1196–1204 (2012)
Meilă, M.: Comparing clusterings by the variation of information. Learning Theory and Kernel Machines 2777, 173–187 (2003)
Schaeffer, S.E.: Graph clustering. Computer Science Review 1(1), 27–64 (2007)
Shen, Y., Yue, F., McCleary, D.F., Ye, Z., Edsall, L., Kuan, S., Wagner, U., Dixon, J., Lee, L., Lobanenkov, V.V., Ren, B.: A map of the cis-regulatory sequences in the mouse genome. Nature 488, 116–120 (2012)
Tanay, A., Cavalli, G.: Chromosomal domains: epigenetic contexts and functional implications of genomic compartmentalization. Current Opinion in Genetics & Development 23(2), 197–203 (2013)
Yaffe, E., Tanay, A.: Probabilistic modeling of Hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture. Nature Genetics 43(11), 1059–1065 (2011)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Filippova, D., Patro, R., Duggal, G., Kingsford, C. (2013). Multiscale Identification of Topological Domains in Chromatin. In: Darling, A., Stoye, J. (eds) Algorithms in Bioinformatics. WABI 2013. Lecture Notes in Computer Science(), vol 8126. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40453-5_23
Download citation
DOI: https://doi.org/10.1007/978-3-642-40453-5_23
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-40452-8
Online ISBN: 978-3-642-40453-5
eBook Packages: Computer ScienceComputer Science (R0)