Computational Methods for Next-Generation Comparative Genomics

项目总结 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完全理解物种进化的能力方面是有限的。 非编码基因组的功能。特别是，众所周知，基因组被划分为不同的 核内的隔室，如核层和核斑点。这样的核 区间化是高级基因组组织的一个基本特征，与不同的 重要的基因组功能，如DNA复制、计时和转录。不幸的是，到目前为止还没有研究 它直接比较了人类和其他哺乳动物之间的核划分。此外, 目前还没有考虑原子核多种特性的连续性质的计算模型 区划和功能，这是整合全基因组功能基因组数据和 跨物种测量到多个隔室的细胞学距离的数据集。在这个项目中，我们将 开发新的算法和生成新的数据集，以直接解决两个关键问题：(1)如何识别 核区划的进化模式？(2)什么类型的序列进化可能驱动 不同物种间的空间定位变化？拟议中的项目是在 核区划的比较基因组学。我们的具体目标是：(1)开发新的 确定核区划演化模式的概率模型。(2)识别 基于TSA-SEQ和TSA-SEQ的灵长类物种核区划的全基因组进化模式 回复-序号(3)开发将序列特征与核区划联系起来的新算法 通过跨物种比较。这些目标的成功实现将导致新的计算 工具和新的数据集，这将是非常有价值的比较基因组学社区。集成了 新的计算工具和独特的数据集将提供对两者关系的宝贵见解 哺乳动物物种的序列进化和核基因组组织的变化。因此， 拟议的研究有望将比较基因组学推进到一个新的前沿，并提供新的 人类基因组功能研究的前景

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