III: Small: Algorithmic Tools for Spatial Positioning Studies in the Cell Nucleus

III：小：细胞核空间定位研究的算法工具

• 批准号: 1115220
• 负责人: Jinhui Xu
• 金额: $ 50万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1115220&HistoricalAwards=false
• 关键词: III; Small; Algorithmic; Tools; Spatial

Spatial positioning has emerged as a fundamental principle governing nuclear processes. Research on chromosome territories has indicated that the 3-D arrangement of these territories within the architecture of the cell nucleus may be closely linked to genomic function, regulation and cell differentiation. Despite this progress, the degree of non-random arrangement of chromosome territories remains unclear and no overall model at the global level has been proposed. In addition, little is known about the gene positioning inside the chromosome territories and its relationship to gene expression. This project is for developing algorithmic tools to facilitate the study of three important spatial positioning problems, (1) topology of chromosome territory, (2) chromosomes associations and spatial positioning, and (3) topological structures of associated chromosomes territories. The focus of this project is on designing efficient algorithms for several challenging computational problems which are essential for the spatial positioning problems, such as chromatic cone clustering, realization, maximum median graph, and optimal surface extraction.The project will use computational geometry techniques and optimization methods to develop a set of efficient algorithmic tools for the proposed problems. The designed and tested algorithms and techniques will be used as automatic (or semi-automatic) tools to accurately and reliably determine the spatial positioning information of genes and chromosome territories, and further elucidate the coordination of genomic expression. Algorithms from this project are also likely to be used in many other areas as information integration tools and positively impact them. This project could lead to several long term impacts. It could yield a much needed global model for studying the spatial positioning of chromosome territories and genes. The obtained algorithmic and biological results will be used to study and compare the difference of various cancer and normal cells in topological structures and associations of chromosome territories and genes. This could potentially lead to significant biological discoveries and help better understanding the mechanism of diseases (such as cancers) and their relationship to chromosome structures and associations.

空间定位已成为管理核过程的基本原则。对染色体领土的研究表明，在细胞核结构中，这些领土的3-D排列可能与基因组功能，调节和细胞分化紧密相关。尽管取得了这种进步，但染色体领土的非随机布置程度仍不清楚，并且在全球层面尚未提出整体模型。此外，关于染色体领土内的基因定位及其与基因表达的关系知之甚少。 该项目用于开发算法工具，以促进研究三个重要的空间定位问题，（1）染色体区域的拓扑结构，（2）染色体协会和空间定位，以及（3）相关染色体区域的拓扑结构。该项目的重点是针对几个具有挑战性的计算问题设计有效的算法，这些算法对于空间定位问题至关重要，例如色锥集群，实现，最大中值图和最佳的表面提取。设计和测试的算法和技术将用作自动（或半自动）工具，以准确，可靠地确定基因和染色体领土的空间定位信息，并进一步阐明基因组表达的协调。该项目的算法也可能在许多其他领域中用作信息集成工具，并对它们产生积极影响。该项目可能会导致几种长期影响。它可能产生急需的全球模型来研究染色体领土和基因的空间定位。所获得的算法和生物学结果将用于研究和比较染色体领土和基因的拓扑结构和关联中各种癌症和正常细胞的差异。这可能会导致重大的生物学发现，并有助于更好地理解疾病的机制（例如癌症）及其与染色体结构和关联的关系。