دورية أكاديمية
أعرض في EDS

Multi-scale phase separation by explosive percolation with single-chromatin loop resolution.

التفاصيل البيبلوغرافية
العنوان: Multi-scale phase separation by explosive percolation with single-chromatin loop resolution.
المؤلفون: Sengupta K; Center of New Technologies, University of Warsaw, Warsaw, Poland.; Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland., Denkiewicz M; Center of New Technologies, University of Warsaw, Warsaw, Poland.; Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland., Chiliński M; Center of New Technologies, University of Warsaw, Warsaw, Poland.; Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland., Szczepińska T; Center of New Technologies, University of Warsaw, Warsaw, Poland.; Centre for Advanced Materials and Technologies, Warsaw University of Technology, Warsaw, Poland., Mollah AF; Center of New Technologies, University of Warsaw, Warsaw, Poland.; Department of Computer Science and Engineering, Aliah University, Kolkata, West Bengal, India., Korsak S; Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland., D'Souza R; Department of Computer Science, University of California, Davis, USA.; The Santa Fe Institute, Santa Fe, USA., Ruan Y; The Jackson Laboratory for Genomic Medicine, USA., Plewczynski D; Center of New Technologies, University of Warsaw, Warsaw, Poland.; Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland.; Department of Computer Science, University of California, Davis, USA.; The Jackson Laboratory for Genomic Medicine, USA.
المصدر: Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2022 Jul 02; Vol. 20, pp. 3591-3603. Date of Electronic Publication: 2022 Jul 02 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology Country of Publication: Netherlands NLM ID: 101585369 Publication Model: eCollection Cited Medium: Print ISSN: 2001-0370 (Print) Linking ISSN: 20010370 NLM ISO Abbreviation: Comput Struct Biotechnol J Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology
Original Publication: Gothenburg, Sweden : Research Network of Computational and Structural Biotechnology
مستخلص: The 2 m-long human DNA is tightly intertwined into the cell nucleus of the size of 10 μm. The DNA packing is explained by folding of chromatin fiber. This folding leads to the formation of such hierarchical structures as: chromosomal territories, compartments; densely-packed genomic regions known as Topologically Associating Domains (TADs), or Chromatin Contact Domains (CCDs), and loops. We propose models of dynamical human genome folding into hierarchical components in human lymphoblastoid, stem cell, and fibroblast cell lines. Our models are based on explosive percolation theory. The chromosomes are modeled as graphs where CTCF chromatin loops are represented as edges. The folding trajectory is simulated by gradually introducing loops to the graph following various edge addition strategies that are based on topological network properties, chromatin loop frequencies, compartmentalization, or epigenomic features. Finally, we propose the genome folding model - a biophysical pseudo-time process guided by a single scalar order parameter. The parameter is calculated by Linear Discriminant Analysis of chromatin features. We also include dynamics of loop formation by using Loop Extrusion Model (LEM) while adding them to the system. The chromatin phase separation, where fiber folds in 3D space into topological domains and compartments, is observed when the critical number of contacts is reached. We also observe that at least 80% of the loops are needed for chromatin fiber to condense in 3D space, and this is constant through various cell lines. Overall, our in-silico model integrates the high-throughput 3D genome interaction experimental data with the novel theoretical concept of phase separation, which allows us to model event-based time dynamics of chromatin loop formation and folding trajectories.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2022 The Authors.)
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فهرسة مساهمة: Keywords: 3D genomics; Chromatin folding; Compartmentalisation; Loop extrusion; Networks; Percolation; Phase separation; Scalar parameter
تواريخ الأحداث: Date Created: 20220721 Latest Revision: 20230916
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9283880
DOI: 10.1016/j.csbj.2022.06.063
PMID: 35860407
قاعدة البيانات: MEDLINE
الوصف
تدمد:2001-0370
DOI:10.1016/j.csbj.2022.06.063