OpenNucleome for high resolution nuclear structural and dynamical modeling DOI Creative Commons
Zhuohan Lao, Kartik Kamat, Zhongling Jiang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 18, 2023

Abstract The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles interpreting observations by reconstructing high-resolution ensembles uncovering principles. However, absence standardized tools poses challenges for furthering investigations. We present OpenNucleome—an open-source software designed conducting GPU-accelerated molecular dynamics simulations nucleus. OpenNucleome offers particle-based representations chromosomes at a resolution 100 KB, encompassing lamina, nucleoli, speckles. This furnishes highly accurate models architecture, affording means dynamic condensate formation, fusion, exploration non-equilibrium effects. applied uncover mechanisms driving emergence “fixed points” within nucleus—signifying genomic loci robustly anchored proximity specific bodies functional purposes. anchoring remains resilient even amidst fluctuations chromosome radial positions shapes individual cells. Our findings lend support zoning model that elucidates genome functionality. anticipate serve as tool investigations, streamlining mechanistic explorations enhancing interpretation observations.

Language: Английский

Chromatin structures from integrated AI and polymer physics model DOI Creative Commons
E Schultz, Soren Kyhl, Rebecca Willett

et al.

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(4), P. e1012912 - e1012912

Published: April 9, 2025

The physical organization of the genome in three-dimensional space regulates many biological processes, including gene expression and cell differentiation. Three-dimensional characterization structure is critical to understanding these processes. Direct experimental measurements are challenging; computational models chromatin therefore necessary. We develop an approach that combines a particle-based polymer model, molecular simulation, machine learning efficiently accurately estimate from indirect measures structure. More specifically, we introduce new where interaction parameters model extracted Hi-C data using graph neural network (GNN). train GNN on simulated underlying avoiding need for large quantities data. resulting estimates structures across all chromosomes several lines despite being trained almost exclusively proposed can be viewed as general framework combining modeling with learning, it could extended integrate additional modalities. Ultimately, achieve accurate high-throughput estimations data, which will necessary methodologies, such single-cell Hi-C, improve.

Language: Английский

Citations

0
OpenNucleome for high-resolution nuclear structural and dynamical modeling DOI Creative Commons
Zhuohan Lao, Kartik Kamat, Zhongling Jiang

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 8, 2024

The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles interpreting observations by reconstructing high-resolution ensembles uncovering principles. However, absence standardized tools poses challenges for furthering investigations. We present OpenNucleome—an open-source software designed conducting GPU-accelerated molecular dynamics simulations nucleus. OpenNucleome offers particle-based representations chromosomes at a resolution 100 KB, encompassing lamina, nucleoli, speckles. This furnishes highly accurate models architecture, affording means dynamic condensate formation, fusion, exploration non-equilibrium effects. applied uncover mechanisms driving emergence ‘fixed points’ within nucleus—signifying genomic loci robustly anchored proximity specific bodies functional purposes. anchoring remains resilient even amidst fluctuations chromosome radial positions shapes individual cells. Our findings lend support zoning model that elucidates genome functionality. anticipate serve as tool investigations, streamlining mechanistic explorations enhancing interpretation observations.

Language: Английский

Citations

2
Transient crosslinking controls the condensate formation pathway within chromatin networks DOI

Zong-Pei Wu,

Kerry Bloom, M. Gregory Forest

et al.

Physical review. E, Journal Year: 2024, Volume and Issue: 109(4)

Published: April 5, 2024

The network structure of densely packed chromatin within the nucleus eukaryotic cells acts in concert with nonequilibrium processes. Using statistical physics simulations, we explore control provided by transient crosslinking structural-maintenance-of-chromosome (SMC) proteins over (i) physical properties and (ii) condensate formation embedded molecular species. We find that density lifetime SMC crosslinks regulate structural relaxation modes tune sol-vs-gel state network, which imparts kinetic pathway to formation. Specifically, lower density, shorter-lived induce sollike networks a droplet-fusion pathway, whereas higher longer-lived gellike an Ostwald-ripening pathway.

Language: Английский

Citations

2
Dynamical phase transition in models that couple chromatin folding with histone modifications DOI
Amogh Sood, Greg Schuette, Bin Zhang

et al.

Physical review. E, Journal Year: 2024, Volume and Issue: 109(5)

Published: May 24, 2024

Genomic regions can acquire heritable epigenetic states through unique histone modifications, which lead to stable gene expression patterns without altering the underlying DNA sequence. However, relationship between chromatin conformational dynamics and stability is poorly understood. In this paper, we propose kinetic models investigate dynamic fluctuations of modifications spatial interactions nucleosomes. Our model explicitly incorporates influence chemical on structural contribution contacts cooperative nature reactions. Through stochastic simulations analytical theory, have discovered distinct steady-state outcomes in different regimes, resembling a dynamical phase transition. Importantly, validated that emergence transition, occurs biologically relevant timescales, robust against variations design parameters. findings suggest viscoelastic properties timescale at it transitions from gel-like liquidlike state significantly impact processes occur along one-dimensional

Language: Английский

Citations

2
OpenNucleome for high resolution nuclear structural and dynamical modeling DOI Open Access
Zhuohan Lao, Kartik Kamat, Zhongling Jiang

et al.

Published: Feb. 8, 2024

The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles interpreting observations by reconstructing high-resolution ensembles uncovering principles. However, absence standardized tools poses challenges for furthering investigations. We present OpenNucleome—an open-source software designed conducting GPU-accelerated molecular dynamics simulations nucleus. OpenNucleome offers particle- based representations chromosomes at a resolution 100 KB, encompassing lamina, nucleoli, speckles. This furnishes highly accurate models architecture, affording means dynamic condensate formation, fusion, exploration non-equilibrium effects. applied uncover mechanisms driving emergence “fixed points” within nucleus—signifying genomic loci robustly anchored proximity specific bodies functional purposes. anchoring remains resilient even amidst fluctuations chromosome radial positions shapes individual cells. Our findings lend support zoning model that elucidates genome functionality. anticipate serve as tool investigations, streamlining mechanistic explorations enhancing interpretation observations.

Language: Английский

Citations

1
OpenNucleome for high-resolution nuclear structural and dynamical modeling DOI Creative Commons
Zhuohan Lao, Kartik Kamat, Zhongling Jiang

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Aug. 15, 2024

The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles interpreting observations by reconstructing high-resolution ensembles uncovering principles. However, absence standardized tools poses challenges for furthering investigations. We present OpenNucleome—an open-source software designed conducting GPU-accelerated molecular dynamics simulations nucleus. OpenNucleome offers particle-based representations chromosomes at a resolution 100 KB, encompassing lamina, nucleoli, speckles. This furnishes highly accurate models architecture, affording means dynamic condensate formation, fusion, exploration non-equilibrium effects. applied uncover mechanisms driving emergence ‘fixed points’ within nucleus—signifying genomic loci robustly anchored proximity specific bodies functional purposes. anchoring remains resilient even amidst fluctuations chromosome radial positions shapes individual cells. Our findings lend support zoning model that elucidates genome functionality. anticipate serve as tool investigations, streamlining mechanistic explorations enhancing interpretation observations.

Language: Английский

Citations

1
OpenNucleome for high resolution nuclear structural and dynamical modeling DOI Open Access
Zhuohan Lao, Kartik Kamat, Zhongling Jiang

et al.

Published: July 1, 2024

The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles interpreting observations by reconstructing high-resolution ensembles uncovering principles. However, absence standardized tools poses challenges for furthering investigations. We present OpenNucleome—an open-source software designed conducting GPU-accelerated molecular dynamics simulations nucleus. OpenNucleome offers particle-based representations chromosomes at a resolution 100 KB, encompassing lamina, nucleoli, speckles. This furnishes highly accurate models architecture, affording means dynamic condensate formation, fusion, exploration non-equilibrium effects. applied uncover mechanisms driving emergence “fixed points” within nucleus—signifying genomic loci robustly anchored proximity specific bodies functional purposes. anchoring remains resilient even amidst fluctuations chromosome radial positions shapes individual cells. Our findings lend support zoning model that elucidates genome functionality. anticipate serve as tool investigations, streamlining mechanistic explorations enhancing interpretation observations.

Language: Английский

Citations

0
Using Free Energy-Based Modeling to Predict Chromatin Loops in the Human Genome DOI
Wayne Dawson, Michał Łaźniewski, Dariusz Plewczyński

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
From Effective Interactions Extracted Using Hi-C Data to Chromosome Structures in Conventional and Inverted Nuclei DOI Creative Commons
Sucheol Shin, Guang Shi, D. Thirumalai

et al.

arXiv (Cornell University), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Contact probabilities between loci, separated by arbitrary genomic distance, for a number of cell types have been reported using genome-wide chromosome conformation capture (Hi-C) experiments. How to extract the effective interaction energies active euchromatin (A) and inactive heterochromatin (B) directly from experimental data, without an underlying polymer model, is unsolved. Here, we first calculate pairwise (A-A, B-B, or A-B) interphase chromosomes based on Hi-C data concept Statistical Potential (SP), which assumes that energy two loci proportional logarithm frequency with they interact. Polymer simulations, extracted values $\textit{without any parameter}$, reproduce segregation A B type (compartments), emergence topologically associating domains (TADs), features are prominent in chromosomes. Remarkably, SP automatically satisfy Flory-Huggins phase separation criterion all chromosomes, explains mechanism compartment formation Strikingly, simulations accounts pericentromeric constitutive (C-type), show hierarchical structuring high density C-type nuclear center, followed localization being confined periphery, differs expected organization but accord imaging inverted nuclei found photoreceptor rods nocturnal mammals. The proposed parameter free method applications conventional best explained inequality energies.

Language: Английский

Citations

0
OpenNucleome for high resolution nuclear structural and dynamical modeling DOI Creative Commons
Zhuohan Lao, Kartik Kamat, Zhongling Jiang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 18, 2023

Abstract The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles interpreting observations by reconstructing high-resolution ensembles uncovering principles. However, absence standardized tools poses challenges for furthering investigations. We present OpenNucleome—an open-source software designed conducting GPU-accelerated molecular dynamics simulations nucleus. OpenNucleome offers particle-based representations chromosomes at a resolution 100 KB, encompassing lamina, nucleoli, speckles. This furnishes highly accurate models architecture, affording means dynamic condensate formation, fusion, exploration non-equilibrium effects. applied uncover mechanisms driving emergence “fixed points” within nucleus—signifying genomic loci robustly anchored proximity specific bodies functional purposes. anchoring remains resilient even amidst fluctuations chromosome radial positions shapes individual cells. Our findings lend support zoning model that elucidates genome functionality. anticipate serve as tool investigations, streamlining mechanistic explorations enhancing interpretation observations.

Language: Английский

Citations

0