Alignment Tools for the Conserved Domain Database

保守域数据库的比对工具

• 批准号: 7316233
• 负责人: STEPHEN H. BRYANT
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7316233
• 关键词: Alignment; Tools; Conserved; Domain; Database

This project covers two inter-related software development efforts. Both are intended to support curators as well as users of the Conserved Domain Database, CDD, as described separately in project LM000161-04. The first effort entails the development and testing of algorithms intended to produce accurate alignments for diverse protein sequences. The second effort involves development of interactive user-friendly tools for aligning large numbers of homologous but diverse protein sequence fragments, and for identifying the subfamily structure within such a protein domain super-family. Development of structure-based alignment algorithms builds upon our group's earlier work on protein threading, a set of structure prediction methods based on the detection of distant homologous relationships. These methods "thread" a protein sequence through a structural template, scoring alternative alignments by energy calculations, using contact potentials, and a sequence profile derived from the protein family of the template. The success of these methods was demonstrated at the 1998 CASP3 workshop, where the NCBI team was awarded "first place" in structure prediction by fold recognition, among over 90 international groups entering the competition. To adapt these methods to the high throughput alignment as needed by CDD curators we have developed more efficient versions of the block-alignment algorithm used in threading. Earlier work has shown that this method produces alignments accurate enough for identification of conserved functional sites, and that information loss relative to the original threading method is minimal. An automated multiple-alignment refinement algorithm, which iteratively applies structure-based alignment on one row at a time, has been thoroughly tested. Its performance suggests that it will benefit the CDD curation effort, and the algorithm is being implemented in Cn3D, a major component of CDD curation software. Cn3D already contains the basic version of the block alignment tool. This software is in daily use by the CDD curator team, and a version with this extended alignment functionality has been widely distributed. Further work has focused on development of the CDTree alignment hierarchy editing system, which is also in daily use by the CDD curator team. This software implements a suite of tools for molecular evolutionary analysis of protein families in an interactive package. It supports generation of phylogenetic sequence trees using several algorithms from the literature, linked to displays of organism taxonomy trees and summaries of overall protein domain architecture. The software also supports an integrated "update" procedure that automatically searches the daily-updated sequence and structure databases for new members of each family, selecting non-redundant representatives of new similarity and/or taxonomy groups. The CDTree subfamily hierarchy editor communicates seamlessly with the Cn3D alignment editor, allowing curator-users to easily detect and correct "outliers" caused by alignment or sequence errors. While designed for needs of CDD curators, CDTree may also be used as a simple viewer, showing in intuitive graphical displays the sequence, taxonomic and functional diversity within a CDD family hierarchy. This year CDTree has been exhaustively tested and public release is imminent, together with a new, compatible version of Cn3D. CDD?s web-services are ready to support visualization of phylogenetic sequence trees, which provide evidence for domain hierarchies as defined by CDD curators. CDD?s web-services are also ready to support download and analysis of CD hierarchies, using CDTree as a helper application on the user?s computer. CDTree?s integrated ?update? procedure provides a novel interface to NCBI?s PSI-BLAST program, which lets users search the protein database with customized position-specific score matrices, after providing an opportunity to analyze and refine the intermediate family alignment models with a variety of tools. We are working with the BLAST group to provide direct CDTree launch capability from BLAST results pages, as generated by the BLAST web services.

这个项目包括两个相互关联的软件开发工作。两者都旨在支持保存域数据库CDD的管理员和用户，如项目LM 000161 -04中单独描述的那样。第一项工作需要开发和测试旨在为不同蛋白质序列产生精确比对的算法。第二项工作涉及开发交互式用户友好的工具，用于比对大量同源但不同的蛋白质序列片段，并用于识别这种蛋白质结构域超家族内的亚家族结构。 基于结构的比对算法的开发建立在我们小组早期关于蛋白质线程的工作基础上，这是一套基于远距离同源关系检测的结构预测方法。这些方法将蛋白质序列“穿线”通过结构模板，通过能量计算、使用接触电势和源自模板的蛋白质家族的序列谱来对备选比对进行评分。这些方法的成功在1998年的CASP 3研讨会上得到了展示，NCBI团队在90多个参加比赛的国际团体中获得了折叠识别结构预测的“第一名”。为了使这些方法适应CDD管理员所需的高吞吐量对齐，我们开发了线程中使用的块对齐算法的更高效版本。早期的工作表明，这种方法产生的比对足够准确，可以识别保守的功能位点，并且相对于原始穿线方法的信息损失很小。一个自动化的多对齐细化算法，迭代地应用基于结构的对齐一次一行，已经过彻底的测试。它的性能表明，它将有利于CDD策展工作，该算法正在CDD策展软件的主要组件Cn 3D中实现。Cn 3D已经包含块对齐工具的基本版本。CDD策展人团队每天都在使用该软件，具有此扩展对齐功能的版本已广泛分发。 进一步的工作集中在CDTree对齐层次编辑系统的开发上，该系统也是CDD策展人团队日常使用的。该软件实现了一套工具的蛋白质家族的分子进化分析在一个互动的包。它支持使用文献中的几种算法生成系统发育序列树，与生物分类树的显示和整体蛋白质结构域架构的总结相关联。该软件还支持一个集成的“更新”程序，该程序自动搜索每日更新的序列和结构数据库中每个家族的新成员，选择新的相似性和/或分类组的非冗余代表。CDTree子家族层次编辑器与Cn 3D比对编辑器无缝通信，允许管理员用户轻松检测和纠正由比对或序列错误引起的“离群值”。虽然CDTree是为满足CDD管理者的需求而设计的，但它也可以用作一个简单的查看器，以直观的图形显示CDD家族层次结构中的序列、分类和功能多样性。 今年，CDTree已经过详尽的测试，即将公开发布，同时发布一个新的兼容版本的Cn 3D。CDD？的Web服务已经准备好支持系统发育序列树的可视化，这为CDD管理员定义的域层次结构提供了证据。CDD？的网络服务也准备好支持下载和分析的CD层次结构，使用CDTree作为一个助手应用程序的用户？的电脑。CDTree？综合？最新消息？程序为NCBI提供了一个新颖的界面？的PSI-BLAST程序，它允许用户搜索蛋白质数据库与定制的位置特异性得分矩阵，提供了一个机会，分析和完善中间家族比对模型与各种工具。我们正在与BLAST小组合作，从BLAST结果页面提供直接的CDTree启动功能，该页面由BLAST Web服务生成。

项目成果

CDD: a Conserved Domain Database for protein classification.

• DOI: 10.1093/nar/gki069
• 发表时间: 2005-01-01
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Marchler-Bauer A;Anderson JB;Cherukuri PF;DeWeese-Scott C;Geer LY;Gwadz M;He S;Hurwitz DI;Jackson JD;Ke Z;Lanczycki CJ;Liebert CA;Liu C;Lu F;Marchler GH;Mullokandov M;Shoemaker BA;Simonyan V;Song JS;Thiessen PA;Yamashita RA;Yin JJ;Zhang D;Bryant SH
• 通讯作者: Bryant SH

Database resources of the National Center for Biotechnology Information.

• DOI: 10.1093/nar/gkq1172
• 发表时间: 2011-01
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Sayers EW;Barrett T;Benson DA;Bolton E;Bryant SH;Canese K;Chetvernin V;Church DM;DiCuccio M;Federhen S;Feolo M;Fingerman IM;Geer LY;Helmberg W;Kapustin Y;Landsman D;Lipman DJ;Lu Z;Madden TL;Madej T;Maglott DR;Marchler-Bauer A;Miller V;Mizrachi I;Ostell J;Panchenko A;Phan L;Pruitt KD;Schuler GD;Sequeira E;Sherry ST;Shumway M;Sirotkin K;Slotta D;Souvorov A;Starchenko G;Tatusova TA;Wagner L;Wang Y;Wilbur WJ;Yaschenko E;Ye J
• 通讯作者: Ye J