Student Theses and Dissertations
Date of Award
2025
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Viviana I. Risca
Keywords
chromatin, nucleosomes, mesoscale, structure inference, Micro Capture-C (MCC), Bayesian modeling
Abstract
The spatial organization of chromatin fiber at the level of several nucleosomes–the mesoscale–is an area of active study. Recent results have shown that it differs between functional states, affects higher orders of chromosome organization, and is likely involved in transcriptional control. However, the heterogeneity of nucleosome positioning and histone variant composition in cells as well as the high density of chromatin in situ make the mesoscale difficult to study. Recent methodological advances have made it possible to derive nucleosome-resolution three-dimensional contact information directly from cells. We therefore sought to develop a structural inference tool for inferring mesoscale chromatin structures consistent with such contact data sets. We have built a Bayesian inference framework that combines a simplified worm-like chain model of DNA and steric interactions between nucleosomes with a pseudopotential that represents the structure's fit to experimental data. We show how this framework can be used to fit oligonucleosome structures to high-coverage Region Capture Micro-C data at several-kilobase regions of interest, evaluate the goodness-of-fit, and discuss how the framework's modularity could lead to promising future work with other types of experimental data. Additionally, we show preliminary data from radiation simulations that will be used to develop models for Radiation-Induced Correlated Cleavage experiments, which will also be incorporated into the structural inference model in future work.
License and Reuse Information
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
West, Devany Walsh, "Towards Models Mesoscale Chromatin Structure and Radiative DNA Damage via Computational Simulation" (2025). Student Theses and Dissertations. 830.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/830
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy