An Interactive Volumetric Atlas of the Mouse Brain

描述(申请人提供)：生物医学界目前面临的一个日益严重的挑战是对神经系统基因组学有足够详细的功能洞察，以了解人类疾病，得出新的治疗方法，并发现新的药物。发现不同实验条件下大脑局部细胞群中基因活性的变化，可以极大地扩大对基因产物如何相互作用以及它们如何影响生物过程和人类疾病的知识。评估空间基因表达变化的一种方法是将数据集注册到一个公共领域--一个图集--其中可以系统地评估实验变化。提高配准的准确性可以在更小的功能特征之间进行比较。该项目的目标是开发一种新的小鼠脑3D图谱和相应的信息学工具，从而对基因表达图像数据集进行更强大的比较。具体目标是：1.开发多材料体积细分网格技术，构建可变形的成年小鼠脑自适应分辨率三维图谱。2.实现了三维地图集对体数据集的交互式配准，并验证了配准的准确性。3.使用收集的一组实验数据评估3D图谱的比较能力，以更好地了解人类遗传性疾病Rett综合征的分子机制。与公共卫生相关：该项目将开发新的软件工具，使研究人员能够更好地了解人类发育和人类疾病潜在的生物过程，可能导致新的治疗方法。这些工具包括一种数字表示基于体积的信息的新技术，该技术可以改进数据集之间的比较，一种将小鼠大脑中基因活动的大规模图像数据放入这种新表示中的方法，以及以高分辨率对这些数据进行比较的方法。

DESCRIPTION (provided by applicant): A growing challenge currently faced by the biomedical community is to gain functional insights into the genomics of the nervous system in sufficient detail to understand human disease, derive novel therapies, and discover new drugs. Discovering changes in gene activity in localized cell populations of the brain under different experimental conditions can significantly expand the knowledge of how gene products interact as well as how they affect biological processes and human disease. One approach to assess changes in spatial gene expression is to register the datasets into a common domain - an atlas - in which experimental alterations can be assessed systematically. Increasing the accuracy of registration enables comparisons between even smaller functional features. The goal of this project is to develop a novel 3D atlas of the mouse brain and corresponding informatics tools that will lead to more powerful comparisons of gene expression image datasets. The specific aims are: 1. Develop multimaterial volumetric subdivision mesh technology and construct a deformable adaptive resolution 3D atlas of the adult mouse brain. 2. Achieve interactive registration of the 3D atlas to volumetric datasets and validate accuracy of registration. 3. Assess the comparison capabilities of the 3D atlas using a set of experimental data collected to better understand the molecular mechanisms of the human genetic disorder Rett Syndrome. PUBLIC HEALTH RELEVANCE: This project will develop new software tools that will enable researchers to better understand the biological processes underlying human development and human diseases, potentially leading to new therapies. These tools include a new technique for digitally representing volume-based information that can improve comparisons between sets of data, a method for placing large-scale image data of gene activity in the mouse brain into this new representation, and the means to perform comparisons of this data at high resolution.