Data-Driven Polymer Model for Mechanistic Exploration of Diploid Genome Organization
| Autor: | Bradley E. Bernstein, Martin J. Aryee, Alejandro Reyes, Bin Zhang, Sarah E. Johnstone, Yifeng Qi |
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| Rok vydání: | 2020 |
| Předmět: |
Computer science
Polymers Cellular differentiation Biophysics Computational biology Biology Genome Chromosomes 03 medical and health sciences 0302 clinical medicine Homologous chromosome Humans Chromosome Positioning 030304 developmental biology Genomic organization Cell Nucleus 0303 health sciences Centromere clustering Genome Human Chromosome Articles Genome structure Diploidy Human genome Ploidy Nuclear localization sequence 030217 neurology & neurosurgery |
| Zdroj: | Biophys J |
| ISSN: | 1542-0086 |
| Popis: | Chromosomes are positioned non-randomly inside the nucleus to coordinate with their transcriptional activity. The molecular mechanisms that dictate the global genome organization and the nuclear localization of individual chromosomes are not fully understood. We introduce a polymer model to study the organization of the diploid human genome: it is data-driven as all parameters can be derived from Hi-C data; it is also a mechanistic model since the energy function is explicitly written out based on a few biologically motivated hypotheses. These two features distinguish the model from existing approaches and make it useful both for reconstructing genome structures and for exploring the principles of genome organization. We carried out extensive validations to show that simulated genome structures reproduce a wide variety of experimental measurements, including chromosome radial positions and spatial distances between homologous pairs. Detailed mechanistic investigations support the importance of both specific inter-chromosomal interactions and centromere clustering for chromosome positioning. We anticipate the polymer model, when combined with Hi-C experiments, to be a powerful tool for investigating large scale rearrangements in genome structure upon cell differentiation and tumor progression. |
| Databáze: | OpenAIRE |
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