Computational Methods for Next-Generation Comparative Genomics

下一代比较基因组学的计算方法

• 批准号: 9765970
• 负责人: Jian Ma
• 金额: $ 43.36万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765970
• 关键词: 3-Dimensional; Address; Algorithms; CRISPR/Cas technology; Cell Nucleus; Cells; Communities; Complement; Computer Simulation; Computing Methodologies; Crete; Cytology; DNA Insertion Elements; DNA Replication Timing; Data Set; Development; Disease; Evolution; Genetic Transcription; Genome; Genomics; Health; Human; Human Biology; Human Genome; Imagery; Knowledge; Lamin Type B; Link; Machine Learning; Mammals; Maps; Measures; Mediating; Methodology; Methods; Mission; Modeling; Molecular Profiling; Nature; Nuclear; Nuclear Lamina; Outcome; Pattern; Phenotype; Primates; Psyche structure; Public Health; Research; Signal Transduction; Statistical Models; Techniques; Time; Translating; United States National Institutes of Health; Untranslated RNA; base; comparative genomics; computerized tools; frontier; functional genomics; genetic variant; genome-wide; genomic data; improved; insight; mental function; next generation; novel; predictive modeling

PROJECT SUMMARY Recent advances in regulatory genomics, especially 3D genome organization in cell nucleus, suggest that existing methods for cross-species comparisons are limited in their ability to fully understand the evolution of non-coding genome function. In particular, it is known that genomes are compartmentalized to distinct compartments in the nucleus such as nuclear lamina and nuclear speckles. Such nuclear compartmentalization is an essential feature of higher-order genome organization and is linked to various important genome functions such as DNA replication timing and transcription. Unfortunately, to date no study exists that directly compares nuclear compartmentalization between human and other mammals. In addition, there are no computational models available that consider the continuous nature of multiple features of nuclear compartmentalization and function, which is critical to integrate genome-wide functional genomic data and datasets that measure cytological distance to multiple compartments across species. In this project, we will develop novel algorithms and generate new datasets to directly address two key questions: (1) How to identify the evolutionary patterns of nuclear compartmentalization? (2) What types of sequence evolution may drive spatial localization changes across species? The proposed project represents the first endeavor in comparative genomics for nuclear compartmentalization. Our Specific Aims are: (1) Developing new probabilistic models for identifying evolutionary patterns of nuclear compartmentalization. (2) Identifying genome-wide evolutionary patterns of nuclear compartmentalization in primate species based on TSA-seq and Repli-seq. (3) Developing new algorithms to connect sequence features to nuclear compartmentalization through cross-species comparisons. Successful completion of these aims will result in novel computational tools and new datasets that will be highly valuable for the comparative genomics community. Integrating the new computational tools and unique datasets will provide invaluable insights into the relationship between sequence evolution and changes in nuclear genome organization in mammalian species. Therefore, the proposed research is expected to advance comparative genomics to a new frontier and provide new perspectives for studying human genome function

项目概要 调控基因组学的最新进展，特别是细胞核中的 3D 基因组组织，表明 现有的跨物种比较方法在充分理解物种进化方面的能力有限。 非编码基因组功能。特别是，众所周知，基因组被划分为不同的 细胞核内的区室，如核纤层和核斑点。这样的核 区室化是高阶基因组组织的一个基本特征，并与各种 重要的基因组功能，例如 DNA 复制计时和转录。不幸的是，迄今为止还没有研究 存在直接比较人类和其他哺乳动物之间的核区室化。此外， 没有可用的计算模型来考虑核的多个特征的连续性质 区室化和功能，这对于整合全基因组功能基因组数据和 测量跨物种多个区室的细胞学距离的数据集。在这个项目中，我们将 开发新颖的算法并生成新的数据集来直接解决两个关键问题：（1）如何识别 核区室化的进化模式？ (2) 可能驱动哪些类型的序列进化 不同物种的空间定位发生变化？拟议的项目代表了在 核区室化的比较基因组学。我们的具体目标是： (1) 开发新产品 用于识别核区室化进化模式的概率模型。 (2) 识别 基于 TSA-seq 的灵长类动物核区室化的全基因组进化模式 复制序列。 (3) 开发新算法将序列特征与核区室化联系起来 通过跨物种比较。成功完成这些目标将带来新的计算方法 对于比较基因组学界来说非常有价值的工具和新数据集。整合 新的计算工具和独特的数据集将为了解两者之间的关系提供宝贵的见解 哺乳动物物种核基因组组织的序列进化和变化。因此， 拟议的研究有望将比较基因组学推进到一个新的领域，并提供新的 研究人类基因组功能的观点