ADVANCED QUANTITATIVE IMAGING FOR DNA PHYSICAL MAPPING

这个多学科项目的广泛目标是推进遗传学 基于计算机系统开发的大比例尺DNA作图研究 用于：1)加快大区域DNA在 单个酵母染色体的规模；2)提高大规模人类 连锁作图。待开发的田野是一种先进的形象- 用于提取信息的采集处理系统 用平板凝胶法分离核酸分子的分级混合物 电泳法。 具体目标是：1)开发一个直接(非照相)系统 用荧光DNA结合染料染色的凝胶成像；2)扩展 适应RFLP作图中使用的自动放射图的系统；3)开发 用于自动化、高分辨率检测的定量成像算法 以及用于确定碎片大小的凝胶带的强度估计 从频带移动性和数据完整性评估；4)应用方法 用于凝胶图像的几何失真补偿，以允许直接 不同方法获得的图像和从不同方法获得的图像的分析比较 不同的实验室；5)开发交互式软件系统 数字化凝胶的快速高效专家解释与分析 最先进的工作站环境中的图像；以及6)评估 系统在满足遗传学研究需求方面的有效性。 方法包括使用先进的CCD成像设备来避免 摄影技术的局限性.应用本地显影图像.估计 改进DNA酶切定量分析的算法 限制酶；使用“翘曲”算法来补偿 电泳性异常.执行接收器工作特性 (REC)和评估数据库研究，以评估检测算法 性能；提供图像处理实用程序以增强凝胶图像 特征；以及通过以下方式辅助凝胶图像的交互解释 基于可接受的窗口和联网构建用户界面 确保软件可移植性和未来出口便利性的标准。 这种三方合作涉及遗传学部，即 计算机科学系(CS)和生物医学计算机 实验室，全部在华盛顿大学。独立资助的政务司司长 Components正在开发一种DNA分析系统，用于维护和 分析大量的DNA片段大小数据和凝胶图像数据 将使用这里提出的系统生成。

The broad goal of this multi-disciplinary project is to advance genetics research in large-scale DNA mapping by developing a computer-based system for: 1) expediting the physical mapping of large regions of DNA on the scale of individual yeast chromosomes; and 2) improving large-scale human linkage mapping. To be developed and fields is an advanced image- acquisition and processing system for extracting information from fractionated mixtures of nucleic-acid molecules separated by slab-gel electrophoresis. Specific aims are to: 1) develop a system for direct (non-photographic) imaging of gels stained with fluorescent DNA-binding dyes; 2) extend the system to accommodate autoradio-grams used in RFLP mapping; 3) develop quantitative-imaging algorithms for automated, high-resolution detection and intensity estimation of gel bands for fragment-size determination from band mobilities and for data-integrity evaluation; 4) apply methods for geometric-distortion compensation of gel images to allow direct analytic comparisons of images obtained by different methods and from different laboratories; 5) develop an interactive software system for rapid and efficient expert interpretation and analysis of digitized gel images in a state-of-the-art workstation environment; and 6) evaluate the system's effectiveness in meeting the needs of the genetic research. Methods include using an advanced CCD imaging device to avoid photographic limitations; applying locally developed image-estimation algorithms to improve quantitative analysis of DNA digested by restriction enzymes; using "warping" algorithms to compensate for electrophoretic aberrancies; performing receiver-operating-characteristic (REC) and evaluation-database studies to assess detection-algorithm performance; providing image-processing utilities for enhancing gel-image features; and aiding interactive interpretation of gel images by constructing a user interface based on accepted windowing and networking standards to ensure software portability and ease of future exportation. This three-way collaboration involves the Department of Genetics, the Department of Computer Science (CS), and the Biomedical Computer Laboratory, all at Washington University. The independently funded CS components is developing a DNA analysis system for maintaining and analyzing large amounts of both DNA-fragment-size data and gel-image data to be generated using the system here proposed.