Center for 3D Structure and Physics of the Genome

项目总结-数据分析和建模 尽管染色体相互作用数据的数量和分辨率不断增长，但我们对物理的理解 染色体组织的基本原理及其与基因组功能的联系仍然有限。 在组件2中提出的染色体相互作用图谱，将提供来自各种 每种方法都针对其自身的方面和染色体组织的规模范围。进一步的进步， 然而，依赖于我们在这些新数据和染色体的3D物理模型之间架起桥梁的能力 可以揭示基因组折叠的原理。 我们将继续开发处理、校正和分析Hi-C-C数据的方法。 基于技术，以及开发染色体组织的聚合物模型 成功地复制了人类和细菌染色体的Hi-C和显微镜数据，并已 能够显示数据中不立即可见的结构元素。在这里，我们建议充分利用 并进一步发展我们基于物理的方法来解决以下几个问题 在理解染色体折叠的生物学机制和物理原理方面的挑战。建模 还将为交互和成像数据的集成提供一个自然的平台。 首先，我们将开发用于处理新的Hi-C-Based产生的数据的计算工具 技术(微-C、高分辨率Hi-C、等位基因特异性Hi-C和单细胞Hi-C)和集成数据 跨范围扩展到集成交互地图。第二，我们将开发计算工具来分析 基于Hi-C新技术制作的互动地图，旨在揭示人类的结构元素 不同尺度的染色体。第三，我们将开发聚合物模型，以验证Hi-C HIPMap显微镜数据的相互作用图，如组件2中所建议的。最后，我们将开发一种 人类染色体组织的综合多尺度聚合物模型，与新的 各个级别的交互数据。所有模型和发现的组织原则都将是系统的 使用组件4中概述的成像、基因组工程和微机械实验进行验证 和5.

PROJECT SUMMARY – Data Analysis and Modeling Despite the growing quantity and resolution of chromosome interaction data our understanding of physical principles underling chromosomal organization and its connection with genomic function remain limited. Mapping of chromosomal interactions proposed in Component 2, will provide large amounts of data from a variety of methods that each address its own aspect and range of scales of chromosomal organization. Further progress, however, relies on our ability to bridge between these new data and 3D physical models of chromosomes that can reveal principles of genome folding. We will continue development of methods for processing, correction and analysis of data from Hi-C- based technologies, as well as development of polymer models of chromosomal organization that have been successful in reproducing Hi-C and microscopy data for human and bacterial chromosomes, and have been able to reveal structural elements not immediately visible in the data. Here we propose to take a full advantage of the new mapping technologies and further develop our physics-based approach to address several challenges in understanding biological mechanisms and physical principles of chromosomes folding. Modeling will also provide a natural platform for integration of interaction and imaging data. First, we will develop computational tools for processing data produced by new Hi-C-based technologies, (micro-C, high-resolution Hi-C, allele-specific Hi-C and single-cell Hi-C), and integrate data across scales into Integrated Interaction Maps. Second, we will develop computational tools to analyze Interaction Maps produced by new Hi-C-based technologies, aiming to reveal structural elements of human chromosomes at different scales. Third, we will develop polymer models that will allow validation of Hi-C interaction maps by HIPMap microscopy data, as proposed in Component 2. Finally, we will develop a comprehensive multi-scale polymer model of human chromosomal organization, comparing it to new interaction data at every scale. All models and discovered principles of organization will be systematically validated using imaging, genome engineering, and micromechanical experiments as outlined in Components 4 and 5.