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Population-based 3D genome structure analysis reveals driving forces in spatial genome organization
- Source :
- Tjong, H; Li, W; Kalhor, R; Dai, C; Hao, S; Gong, K; et al.(2016). Population-based 3D genome structure analysis reveals driving forces in spatial genome organization. Proceedings of the National Academy of Sciences of the United States of America, 113(12), E1663-E1672. doi: 10.1073/pnas.1512577113. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/3711d59m, Proceedings of the National Academy of Sciences of the United States of America, vol 113, iss 12
- Publication Year :
- 2016
- Publisher :
- National Academy of Sciences, 2016.
-
Abstract
- Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.
- Subjects :
- 0301 basic medicine
Genome
Imaging
0302 clinical medicine
Heterochromatin
3D genome organization
Chromosomes, Human
Lymphocytes
Tomography
In Situ Hybridization
In Situ Hybridization, Fluorescence
Genomic organization
Genetics
education.field_of_study
Likelihood Functions
Multidisciplinary
Centromere clustering
Tomography, X-Ray
genome structure modeling
Biological Evolution
Chromatin
centromere clustering
PNAS Plus
Hi-C data analysis
Single-Cell Analysis
Human
Primates
1.1 Normal biological development and functioning
Population
Centromere
Computational biology
Biology
Fluorescence
Chromosomes
Cell Line
03 medical and health sciences
Imaging, Three-Dimensional
human genome
Animals
Humans
Chromosome Positioning
education
Stochastic Processes
Genome, Human
Chromosome
Diploidy
030104 developmental biology
Three-Dimensional
X-Ray
Human genome
Generic health relevance
Metagenomics
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Tjong, H; Li, W; Kalhor, R; Dai, C; Hao, S; Gong, K; et al.(2016). Population-based 3D genome structure analysis reveals driving forces in spatial genome organization. Proceedings of the National Academy of Sciences of the United States of America, 113(12), E1663-E1672. doi: 10.1073/pnas.1512577113. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/3711d59m, Proceedings of the National Academy of Sciences of the United States of America, vol 113, iss 12
- Accession number :
- edsair.doi.dedup.....add9a2c135bd9e436d485dba86d6e69c