Collaborative Research: ABI Innovation: Integrative Analysis of the Anatomic and Genetic Landscapes in the Mouse Brain

赠款授予老自治领大学和东弗吉尼亚医学院，以开发新的计算方法，分析艾伦脑图谱数据集，其中包含最全面的收集基因组规模，细胞分辨率，三维基因表达模式的小鼠大脑。对这些数据的全球分析将阐明哺乳动物大脑的解剖学和遗传学景观，最终导致对大脑功能回路的理解。本计画将发展一类新颖的计算方法，以整合分析小鼠脑的解剖与遗传景观。为了实现全基因组全局计算，本项目将研究用于整合全基因组和全脑结构的分层模型。此外，张量计算技术将被开发用于数据压缩和可视化。通过应用本文提出的先进计算方法获得的见解有可能实现和加速生物学见解，并产生可通过实验验证的假设。特别是，本项目有望在以下领域取得重大进展：（1）通过对基因表达的系统水平分析，对遗传网络进行多维分析，从而了解哺乳动物大脑的结构和发育;（2）了解活跃的、对哺乳动物大脑功能有贡献的分子通路;（3）了解哺乳动物大脑的结构和发育。以及（3）了解基因和分子途径的破坏如何导致小鼠和最终人类大脑的病理学。该项目将在教育和培训学生方面发挥不可或缺的作用。艾伦脑图谱资源已被纳入本科生和研究生课程，作为有吸引力的教学工具。该项目将超越原始数据，从中提取新知识，从而大大丰富现有课程，促进新课程的开发。解剖学和遗传学连接图将被用作创新的教学工具，它们提供了视觉上吸引人的辅助工具和教学各种主题的例子，并为计算机实验室练习提供了机会。教育活动将利用旧自治领大学的顶级远程学习计划，其网站是专门为教育资源有限的人服务。欲了解更多信息，请访问项目网站http://compbio.cs.odu.edu/NSF-ABI/。

Grants are awarded to Old Dominion University and to Eastern Virginia Medical School in order to develop novel computational methods for analyzing the Allen Brain Atlas data set, which contains the most comprehensive collection of genome-scale, cellular-resolution, three-dimensional gene expression patterns of the mouse brain. Global analyses of these data would elucidate the anatomic and genetic landscapes of the mammalian brain, leading ultimately to the understanding of brain functional circuitry. This project will develop a class of novel computational methods for integrative analysis of the anatomic and genetic landscapes in the mouse brain. To enable genome-wide global computation, this project will investigate hierarchical models for incorporating genome-wide and brain-wide structures. Additionally, tensor computation techniques will be developed for data compression and visualization. Insights obtained through the application of advanced computational methods as proposed here have the potential to enable and accelerate biological insights and generate experimentally testable hypotheses. In particular, this project is expected to enable significant progress in the areas of (1) understanding the structure and development of the mammalian brain through the multidimensional analysis of genetic networks that can be identified through systems-level analysis of gene expression, (2) understanding molecular pathways that are active and contribute to the function of the mammalian brain, and (3) understanding how disruptions of genes and thus molecular pathways might contribute to pathologies of mouse and ultimately human brains.The project will play an integral part in educating and training students. The Allen Brain Atlas resources have been integrated into undergraduate and graduate curricula as appealing pedagogical tools. This project will go beyond the raw data by extracting new knowledge from them, thereby significantly enriching current curricula and catalyzing new course development. The anatomic and genetic connectivity maps will be used as innovative pedagogical tools, where they offer visually appealing aids and examples for teaching a variety of topics and provide opportunities for in silico laboratory exercises. The educational activities will leverage Old Dominion University's top-class distance learning program whose sites are specifically designed to serve people with limited educational resources. For more information please visit the project website at http://compbio.cs.odu.edu/NSF-ABI/.