Modeling the 3D Conformation of Genomes

This book provides a timely summary of physical modeling approaches applied to biological datasets that describe conformational properties of chromosomes in the cell nucleus. Chapters explain how to convert raw experimental data into 3D conformations, and how to use models to better understand biophysical mechanisms that control chromosome conformation. The coverage ranges from introductory chapters to modeling aspects related to polymer physics, and data-driven models for genomic domains, the entire human genome, epigenome folding, chromosome structure and dynamics, and predicting 3D genome structure.

Contents Preface vii Contributors xi 1 Chromosome Folding: Contributions of Chromosome Conformation Capture and Polymer Physics 1 Job Dekker Part 1 FIRST-PRINCIPLES MODELS 19 2 Modeling the Functional Coupling between 3D Chromatin Organization and Epigenome 21 Cédric Vaillant and Daniel Jost 3 The Strings and Binders Switch Model of Chromatin 57 Simona Bianco, Andrea M. Chiariello, Carlo Annunziatella, Andrea Esposito, Luca Fiorillo, and Mario Nicodemi 4 Loop Extrusion: A Universal Mechanism of Chromosome Organization 69 Leonid A. Mirny and Anton Goloborodko 5 Predictive Models for 3D Chromosome Organization: The Transcription Factor and Diffusive Loop Extrusion Models 97 C. A. Brackley, M. C. Pereira, J. Johnson, D. Michieletto, and D. Marenduzzo 6 Introducing Supercoiling into Models of Chromosome Structure 115 Fabrizio Benedetti, Dusan Racko, Julien Dorier, and Andrzej Stasiak 7 Structure and Microrheology of Genome Organization: From Experiments to Physical Modeling 139 Andrea Papale and Angelo Rosa 8 Analysis of Chromatin Dynamics and Search Processes in the Nucleus 177 Assaf Amitai and David Holcman 9 Chromosome Structure and Dynamics in Bacteria: Theory and Experiments 207 Marco Gherardi, Vittore Scolari, Remus Thei Dame, and Marco Cosentino Lagomarsino Part 2 DATA -DRIVEN MODELS 231 10 Restraint-Based Modeling of Genomes and Genomic Domains 233 Marco Di Stefano and Marc A. Marti-Renom 11 Genome Structure Calculation through Comprehensive Data Integration 253 Guido Polles, Nan Hua, Asli Yildirim, and Frank Alber 12 Modeling the Conformational Ensemble of Mammalian Chromosomes from 5C/Hi-C Data 285 Guido Tiana and Luca Giorgetti 13 Learning Genomic Energy Landscapes from Experiments 305 Michele Di Pierro, Ryan R. Cheng, Bin Zhang, José N. Onuchic, and Peter G. Wolynes 14 Physical 3D Modeling of Whole Genomes: Exploring Chromosomal Organization Properties and Principles 331 Marco Di Stefano, Jonas Paulsen, Eivind Hovig, and Cristian Micheletti 15 Index 361

Guido Tiana, PhD, is Associate Professor of Theoretical Biophysics at the University of Milano. He obtained the PhD at the Niels Bohr Institute (Copenhagen) in 2000 and since then has worked on the physics of complex systems of biological interest, such as proteins, DNA, RNA, chromosomes and genetic networks. The methods come from the realm of statistical mechanics, making heavy use of computational tools and some experimental work. Luca Giorgetti, PhD, is a group leader at the Friedrich Miescher Institute for Biomedical Research in Basel. He obtained his PhD at the European Institute of Oncology (IEO) and University of Milan followed by a postdoctoral training at the Curie Institute in Paris. He is an expert in combining physical modeling and experimental research in chromosome conformation and transcriptional regulation.