IMAGE BASED PHENOTYPING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目始于犹他州大学埃克尔斯人类遗传学研究所马里奥·卡佩奇博士的实验室。卡佩奇博士的实验室正在研究特定的、诱导性基因异常在小鼠身上的表型表达，该模型已被证明可以深入了解先天性人类疾病的个体发育。传统的小鼠骨骼结构分析需要牺牲研究动物，以及在解剖显微镜下进行骨骼准备和身体检查的劳动密集型、耗时的过程。要进行有意义的统计分析，往往需要数十甚至数百个样本，这意味着巨大的时间和金钱投入。综合生物医学计算中心与Capecchi实验室合作的目标是开发一种更快的、非侵入性的骨骼分析方案，该方案使用三维微型CT的半自动图像处理，而不是对准备好的骨骼标本进行手动测量。我们正在继续开发一套用于定量形态测量的图像分割、测量和可视化算法和软件系统，使我们能够试验新的测量指标，如形状分析，这是准备好的骨骼标本无法实现的。此外，我们预计我们的工具将允许对长度、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(部分渗透性)或被误解为次要影响的基因变化。 多年来，这个项目吸引了从事其他成像方式和各种病理研究的合作者的兴趣，这些疾病包括儿童肿瘤、自闭症和心脏缺陷。特别是，与查尔斯·凯勒实验室(俄勒冈大学健康科学中心)的合作正在扩大形状分析工作。CIBC与凯勒博士的工作主要集中在骨骼表型上，使用的是通过基因敲除创建的小鼠模型。这一过程是使用Seg3D分割3D MicroCT图像集，并使用CIBC软件ShapeWorks、SCIRun和/或ImageVis3D分析和可视化结果。这项工作代表了一种正在进行的小鼠反向遗传学策略，作为确定单个基因对复杂生物过程的贡献的一种方式，例如发育模式。

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.