PATTERN MATCHING IN SEQUENCE & STRUCTURE

蛋白质家族和序列基序的鉴定 作为人类基因组中日益重要的序列信息 项目开始可用。在此支持的早期工作中 奖，我们开发了一种计算基于序列的基序的技术 描述或进化简档(EP)。简而言之，这种方法适合 一组中每个对齐位置的显式进化模型 比对的序列。这个模型描述了最好的进化 二十个氨基酸残基中每一个氨基酸的距离。有限的混合物 然后计算模型，在该模型中，20个可能的 祖先的残留物是根据它产生 在给定进化距离下观察到的分布。在……里面 继续今年的工作，我们正在使用EP方法来建造 丝氨酸/苏氨酸和酪氨酸激酶整个家族的模型。 该项目涉及为每条路线建造多条路线 在五个主要的激酶家族和55个亚家族中，以及 下一代EP。EP是有效的描述/量词 对于蛋白质家族，将使用激酶图谱来分类 新的激酶并为蛋白质提供多个序列比对 SDSC上的激酶资源。持续改进配置文件分析 方法是由软件的这种“试验床”使用产生的。基座 根据去年的经验，我们实施了新的和更多的 用于模式识别的灵活服务器。此服务器SeqWeb是 旨在支持多种模式下的多种应用程序 互动。通过互联网提供最终用户应用程序会带来 各种困难。虽然有些申请可以在 较短的时间段，因此是提供 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 以完成，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。对于传统的交互式 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； 每一步都容易出错，并增加出错的机会。这个 SeqWeb服务器就是为解决这些问题而设计的。 提供临时文件存储，以方便使用系列 节目的数量。本地文件存储还允许系统执行更多 严格控制文件的格式，避免了许多繁琐的格式 由文件传输引入的转换和错误。这也是 为符合以下条件的分析提供投递和拾取交互 需要几分钟以上的时间。此外，SeqWeb还为 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)。这三种交互模式 在提供访问权限方面提供极大的灵活性 申请。当前版本的SeqWeb实现了一系列 与上述进化轮廓方法一起使用的程序： 具体地，多序列比对、序列加权、简档 创建、配置文件数据库搜索(使用Bioccelerator)和 序列和轮廓的比对。SeqWeb还提供访问 本地可用的数据库，以及用于定制显示的工具 路线。明年，SeqWeb将扩展到包括 与NBCR合作开发的Meme和Mast程序，及其 通过添加其他显示和分析来扩展功能 功能。

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.