IMAGE BASED PHENOTYPING

基于图像的表型分析

• 批准号: 8172261
• 负责人: ROSS T WHITAKER
• 金额: $ 11.59万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172261
• 关键词: Algorithms; Animal Experimentation; Autistic Disorder; Biological Process; Biomedical Computing; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer software; Congenital Heart Defects; Development; Funding; Genes; Genetic; Goals; Grant; Growth; Hand; Health Sciences; Human Genetics; Image; Imagery; Institutes; Institution; Investments; Laboratories; Length; Measurement; Metric; Microscope; Minor; Modeling; Molecular Abnormality; Mus; Mutation; Oregon; Pathology; Pattern; Pediatric Neoplasm; Phenotype; Preparation; Process; Protocols documentation; Research; Research Personnel; Resources; Skeleton; Source; Specimen; Structure; Time; United States National Institutes of Health; Universities; Utah; Work; base; density; human disease; image processing; imaging Segmentation; imaging modality; insight; interest; morphometry; mouse model; positional cloning; research study; shape analysis; skeletal; software systems; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project started with the laboratory of Dr. Mario Capecchi at the University of Utah's Eccles Institute of Human Genetics. Dr. Capecchi's laboratory was investigating the phenotypic expression of specific, induced genetic abnormalities in mice, a model that has been shown to provide insight into the ontogeny of congenital human disease. Conventional analysis of mouse skeletal structure requires sacrificing the research animal and a labor-intensive, time-consuming process of skeleton preparation and physical inspection under a dissecting microscope. Many tens or even hundreds of specimens are often required for a meaningful statistical analysis, which represents an enormous investment of time and money. The goal of the Center for Integrative Biomedical Computing collaboration with the Capecchi lab is to develop a faster, non-invasive protocol for skeletal analysis that uses semi-automated image processing of three-dimensional micro-CT rather than hand measurements of prepared skeletal specimens. We are continuing the development of a set of image segmentation, measurement and visualization algorithms and software systems for quantitative morphometry that allow us to experiment with new metrics such as the analysis of shape that would not be possible with prepared skeletal specimens. Furthermore, we expect that our tools will allow for more precise and repeatable measurements for length, density and volume, and therefore give insight into genetic alterations that have previously been described as pleiotropic (partially penetrant) or that have been misinterpreted as minor effects. Over the years this project has gained interest from collaborators working with other imaging modalities and various pathologies including childhood tumors, autism, and heart defects. In particular, collaborative work with the Charles Keller laboratory (University of Oregon Health Sciences Center) is extending the shape analysis work. The work of the CIBC with Dr. Keller has focused primarily on skeletal phenotypes using mouse mice models that have been created through genetic knock outs. The process has been to segment sets of 3D microCT images using Seg3D and to analyze and visualize the results using the CIBC software: ShapeWorks, SCIRun and/or ImageVis3D. This work represents an ongoing strategy of reverse genetics in the mouse as a way of determining the contribution of a single gene to a complex biological process, such as developmental patterning.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 该项目始于犹他大学埃克尔斯人类遗传学研究所 Mario Capecchi 博士的实验室。 卡佩奇博士的实验室正在研究小鼠中特定的诱导性遗传异常的表型表达，该模型已被证明可以提供对人类先天性疾病的个体发育的深入了解。小鼠骨骼结构的传统分析需要牺牲研究动物，并且在解剖显微镜下进行骨骼准备和物理检查的劳动密集型、耗时的过程。进行有意义的统计分析通常需要数十甚至数百个样本，这需要投入大量的时间和金钱。综合生物医学计算中心与卡佩奇实验室合作的目标是开发一种更快、非侵入性的骨骼分析方案，该方案使用三维显微 CT 的半自动图像处理，而不是对准备好的骨骼标本进行手工测量。我们正在继续开发一套用于定量形态测量的图像分割、测量和可视化算法以及软件系统，使我们能够尝试新的指标，例如形状分析，而这对于准备好的骨骼标本来说是不可能的。此外，我们期望我们的工具能够对长度、密度和体积进行更精确和可重复的测量，从而深入了解以前被描述为多效性（部分渗透）或被误解为次要影响的基因改变。 多年来，该项目引起了研究其他成像方式和各种病理学（包括儿童肿瘤、自闭症和心脏缺陷）的合作者的兴趣。 特别是与查尔斯·凯勒实验室（俄勒冈大学健康科学中心）的合作正在扩展形状分析工作。 CIBC 与 Keller 博士的工作主要集中在使用通过基因敲除创建的小鼠模型来研究骨骼表型。 该过程是使用 Seg3D 对 3D microCT 图像集进行分割，并使用 CIBC 软件（ShapeWorks、SCIRun 和/或 ImageVis3D）对结果进行分析和可视化。 这项工作代表了小鼠反向遗传学的持续策略，作为确定单个基因对复杂生物过程（例如发育模式）的贡献的一种方法。