COMPUTATIONAL BIOCHEMISTRY

计算生物化学

• 批准号: 6324796
• 负责人: KIM K BALDRIDGE
• 金额: $ 20.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6324796
• 关键词: biomedical resource; computers; genome; nucleic acids; proteins; statistics /biometry; technology /technique

Identification of protein families and the sequence motifs is increasingly important as sequence information from the Human Genome Project begins to be available. In earlier work supported by this award, we developed a technique for calculating sequence based motif descriptions or evolutionary profiles (EP). Briefly, this method fits an explicit evolutionary model to each aligned position in a group of aligned sequences. This model describes the best evolutionary distance for each of the twenty amino acid residues. A finite mixture model is then calculated in which each of the twenty possible ancestral residues is weighted by its probability of giving rise to the observed distribution at the given evolutionary distance. In continuing work this year we are using the EP method to construct models for the entire family of serine/threonine and tyrosine kinases. This project involves the construction of multiple alignments for each of the five major kinase families and 55 subfamilies, and the subsequent generation of EP. EP are effective description/classifiers for protein families, and the kinase profiles will be used to classify novel kinases and provide multiple sequence alignments for the Protein Kinase Resource at SDSC. Continual improvements to profile analysis methods are resulting from this "testbed" use of the software. Based on experience from the last year we have implemented a new and more flexible server for pattern recognition. This server, SeqWeb, is designed to support multiple application in a variety of modes of interaction. Providing end-user applications via the internet poses a variety of difficulties. While some applications can be completed in short periods of time, and thus are good candidates for providing services via an interactive web page, others require minutes or hours to finish and must therefore employ a different interactive mode. Furthermore, many applications require inputs from other programs, or provide inputs to other programs. For a traditional interactive server, this requires frequent copying of data to and from the server; each step is error prone and increases the chance of errors. The SeqWeb server has been designed to address many of these issues. Temporary file storage is provided to facilitate the use of a series of programs. Local file storage also allows the system to more closely control the format of files, and obviates many tedious format conversions and errors introduced by file transfers. This also provides for a drop-off and pick-up interaction for analyses that require more than a few minutes. In addition, SeqWeb provides for the return of results by web pages (traditional mode) and by email (similarly to the MEME/MAST server). These three modes of interaction provide greatly enhance flexibility in provided access to applications. The current version of SeqWeb implements a series of programs for use with the evolutionary profile method described above: specifically, multiple sequence alignment, sequence weighting, profile creation, profile database searching (using Bioccelerator), and alignment of sequences and profiles. SeqWeb also provides ac cess to databases available locally, and tools for the custom display of alignments. In the next year SeqWeb will be extended to include the MEME and MAST programs developed in collaboration with NBCR, and its functionality extended by the addition of other display and analysis functions.

蛋白质家族和序列基序的鉴定是 来自人类基因组的序列信息变得越来越重要 项目开始可用。 在此支持的早期工作中 获奖，我们开发了一种计算基于序列的基序的技术 描述或进化概况（EP）。 简单来说，这个方法适合 一组中每个对齐位置的显式进化模型 对齐的序列。 这个模型描述了最好的进化 二十个氨基酸残基中每一个的距离。 有限混合 然后计算模型，其中二十种可能的每一种 祖先残留物的权重取决于其产生的概率 在给定进化距离下观察到的分布。 在 今年继续工作我们正在使用EP方法来构建 整个丝氨酸/苏氨酸和酪氨酸激酶家族的模型。 该项目涉及为每个项目构建多个路线 五个主要激酶家族和 55 个亚家族，以及 EP 的后续生成。 EP 是有效的描述/分类器 对于蛋白质家族，激酶谱将用于分类 新型激酶并为蛋白质提供多序列比对 SDSC 的激酶资源。 持续改进轮廓分析 方法是从软件的“测试平台”使用中产生的。 基于 根据去年的经验，我们实施了新的、更多的 用于模式识别的灵活服务器。 该服务器 SeqWeb 是 旨在支持多种模式下的多种应用 相互作用。 通过互联网提供最终用户应用程序构成了 各种困难。 虽然有些申请可以在 时间很短，因此是提供的良好候选者 通过交互式网页提供服务，其他服务则需要几分钟或几小时 完成，因此必须采用不同的交互模式。 此外，许多应用程序需要来自其他程序的输入，或者 为其他程序提供输入。 对于传统的互动 服务器，这需要频繁地将数据复制到服务器或从服务器复制数据； 每个步骤都容易出错，并且会增加出错的机会。 这 SeqWeb 服务器旨在解决其中许多问题。 提供临时文件存储，方便系列产品的使用 的程序。 本地文件存储还可以让系统更 严格控制文件格式，省却许多繁琐的格式 文件传输引入的转换和错误。 这也 为分析提供下车和上车互动 需要几分钟以上。 此外，SeqWeb 还提供 通过网页（传统模式）和电子邮件返回结果 （类似于 MEME/MAST 服务器）。 这三种交互方式 极大地增强了访问的灵活性 应用程序。 当前版本的 SeqWeb 实现了一系列 与上述进化概况方法一起使用的程序： 具体来说，多序列比对、序列加权、概况 创建、配置文件数据库搜索（使用 Bioccelerator）以及 序列和概况的比对。 SeqWeb 还提供访问 本地可用的数据库以及用于自定义显示的工具 对齐。 明年 SeqWeb 将扩展至包括 与 NBCR 合作开发的 MEME 和 MAST 项目及其 通过添加其他显示和分析来扩展功能 功能。