Center for 3D Structure and Physics of the Genome

基因组 3D 结构和物理中心

基本信息

批准号：
9021491
负责人：
Leonid A Mirny
金额：
$ 34.04万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9021491
关键词：
Accounting Address Agreement Alleles Bacterial Chromosomes Binding Biological Cell Cycle Cells Characteristics Chromatin Chromosome Structures Chromosomes Data Data Analyses Development Elements Epigenetic Process Frequencies Functional Imaging Gene Expression Genome Genome engineering Genomics Human Human Chromosomes Image Imaging technology Knowledge Maps Mechanics Methods Microscopy Mitotic Chromosome Modeling Molecular Morphology Pattern Physical condensation Physics Polymers Positioning Attribute Process Property Proteins Relative (related person)Resolution Signal Transduction Structure Techniques Technology Validation Variant base cell type comparative computerized data processing computerized tools data integration data modeling method development model building physical model research study three dimensional structure tool

项目摘要

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.

项目摘要 – 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，我们对物理学的理解染色体组织的原理及其与基因组功能的联系仍然有限。组件 2 中提出的染色体相互作用图谱将提供来自各种来源的大量数据每种方法都解决了染色体组织自身方面和范围的进一步进展，然而，我们依靠我们在这些新数据和染色体 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-数据的方法基于技术，以及染色体组织聚合物模型的开发成功复制了人类和细菌染色体的 Hi-C 和显微镜数据，并已能够揭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。新的测绘技术并进一步开发我们基于物理的方法来解决几个问题理解染色体折叠的生物机制和物理原理的挑战。还将提供一个用于集成交互和成像数据的自然平台。首先，我们将开发计算工具来处理新的基于 Hi-C 的数据产生的数据技术（micro-C、高分辨率 Hi-C、等位基因特异性 Hi-C 和单细胞 Hi-C），并集成数据其次，我们将开发计算工具来分析。基于 Hi-C 的新技术生成的交互图，旨在揭示人类的结构元素第三，我们将开发能够验证 Hi-C 的聚合物模型。如组件 2 中所提议的，通过 HIPMap 显微镜数据绘制交互图。最后，我们将开发一个人类染色体组织的综合多尺度聚合物模型，将其与新的所有规模的交互数据和发现的组织原则都将被系统化。使用成像、基因组工程和微机械实验进行验证，如组件 4 中所述和 5.