COMPUTER MANAGEMENT OF HIGH RESOLUTION PHYSICAL DNA MAPS

高分辨率物理 DNA 图谱的计算机管理

• 批准号: 2332368
• 负责人: WILL GILLETT
• 金额: $ 33.87万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2332368
• 关键词: DNA; computer program /software; computer system design /evaluation; information systems; restriction mapping

The overall objective of this research has been and continues to be the development of computer techniques for constructing high-resolution restriction maps, pushing the boundary of automated construction as far as possible. In this phase of the activity, the focus will turn to: (a) whole-chromosome mapping at the cosmid level, eliminating a dependence on prior mapping of the chromosome at the YAC level, and (b) the transfer of Multile-Complete-Digestion (MCD) high-resolution restriction-fragment mapping techniques to creating sequence-ready maps. These activities are in direct support of: (i) decreasing the human-intensive component required for mapping and sequencing, (ii) increasing the quality and continuity of the maps and sequences produced, and (iii) reducing the overall time and cost of mapping and sequencing. Computer techniques that we have already developed to produce restriction maps of YACs with cosmid clones will be refined to address whole- chromosome mapping with cosmids and enhanced to producing sequence-ready maps of small-insert clones, such as M13 and plasmids. We plan to allow synchronizing the sequence-ready maps with the "parent" maps composed of cosmids, using tie-point landmarks common to both. Our specific aims are to: 1) Upgrade our current mapping techniques to produce a system capable of perform whole-chromosome mapping at the cosmid level. The primary mapping technique for achieving this will be the construction of a new bridging MCD approach. 2) Transfer the high-resolution restriction-mapping technology that has been developed to the construction of sequence-ready maps of at the small-insert clone level. This transfer will include enhancements of the basic MCD mapping technique to take advantage of forms of data other than complete- restriction-fragment data, such as sequence data and end-labeled-fragment data. 3) Enhance supporting techniques to push automated mapping as far as possible. This will include the development and integration of a number of independent techniques which are currently done by human-intensive activities. 4) Convert the system to a true object-oriented paradigm so that its components are modifiable, extendible, and embeddable in production environments. This will be achieved by converting the present functionality to C++, refurbishing the code during the conversion.

这项研究的总体目标一直是并将继续是 计算机技术的发展用于构建高分辨率 限制图，将自动化施工的边界推得更远 尽可能。在这一阶段的活动中，重点将转向： (a) 粘粒水平的全染色体作图，消除依赖性 先前在 YAC 水平上对染色体作图，以及 (b) 转移 多重完全消化 (MCD) 高分辨率限制性片段 用于创建序列就绪图谱的映射技术。这些活动是 直接支持： (i) 减少人力密集部分 作图和测序所需的，(ii) 提高质量和 所产生的地图和序列的连续性，以及（iii）减少 绘图和测序的总时间和成本。 我们已经开发出用于产生限制的计算机技术 带有粘粒克隆的 YAC 图谱将得到完善，以解决整体问题 使用粘粒进行染色体作图并增强以产生序列就绪 小插入克隆的图谱，例如 M13 和质粒。我们计划允许 将序列就绪图谱与由以下组成的“父”图谱同步 粘粒，使用两者共有的连接点标志。 我们的具体目标是： 1）升级我们当前的测绘技术，以产生一个能够 在粘粒水平上进行全染色体作图。 实现这一目标的主要映射技术将是 构建新的桥接MCD方法。 2) 转让已有的高分辨率酶切图技术 已开发用于构建序列就绪图谱 小插入克隆水平。 此次转让将包括基本 MCD 映射的增强 技术利用除完整数据之外的形式 限制性片段数据，例如序列数据和末端标记片段 数据。 3）加强支撑技术，推动自动化测绘 可能的。 这将包括开发和整合一些 目前由人力密集型完成的独立技术 活动。 4) 将系统转换为真正的面向对象范式，使其 组件可修改、可扩展且可嵌入生产中 环境。 这将通过将现有功能转换为 C++ 来实现， 在转换期间刷新代码。