RNA 3D Motif Search, Atlas, and Prediction from Sequence

RNA 3D 基序搜索、图谱和序列预测

• 批准号: 8515455
• 负责人: Craig L Zirbel
• 金额: $ 29.42万
• 依托单位: BOWLING GREEN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-10 至 2014-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8515455
• 关键词: Archives; Atlases; Attention; Base Pairing; Biomedical Research; Code; Collaborations; Communities; Computers; Data; Data Set; Databases; Frequencies; Functional RNA; Genes; Genome; Growth and Development function; Human; Human Genome; Internet; Ions; Language; Measures; Mediating; Methodology; Methods; Modeling; Names; Nucleic Acid Databases; Nucleic Acids; Nucleotides; Online Systems; Ontology; Pattern; Procedures; RNA; RNA Sequences; Recurrence; Reproduction; Research Personnel; Resources; Sequence Homologs; Services; Shapes; Statistical Models; Structural Biologist; Structure; Update; Validation; Variant; Vertebral column; Water; Work; base; improved; inorganic phosphate; insertion/deletion mutation; macromolecule; member; programs; public health relevance; statistics; three dimensional structure; tool; web services

DESCRIPTION (provided by applicant): We propose to make the growing body of experimental three-dimensional (3D) RNA structure data more useful to biomedical researchers by providing improved methods to integrate 3D RNA structure with sequence and other experimental data. New annotation tools and services developed in this project will be integrated into the Nucleic Acid Database (NDB) which will provide a platform for disseminating project results. Among the expected benefits are better methods for 1) predicting 3D structures of functional RNA motifs from sequence, 2) searching for non-coding RNA genes in genomes, and 3) improving alignments of homologous RNA sequences. We focus attention on recurrent, modular RNA 3D motifs, which occur in a wide variety of structured RNA molecules, and which give RNA its distinctive 3D shape. This includes hairpin loops, internal loops, junction loops, and tertiary interaction motifs. We will develop systematic methods to identify, classify, and name recurrent RNA 3D motifs and to define search criteria to reliably find instances of each motif in 3D structures. An annotation procedure will be established so that new motifs are rapidly identified in new structures and vetted in collaboration with other members of the RNA Ontology Consortium. All experimental RNA 3D structures will be annotated with lists of motifs. A Motif Atlas will be created to make information about 3D motif instances in structures available to users. This new Atlas containing the annotation of motifs will be added to the Nucleic Acid Database (NDB), a web resource containing structural and functional annotation of nucleic acid containing macromolecules. An update procedure will be developed such that motif data and Atlas entries will automatically be added to the NDB as new RNA structures become available in the PDB archive. We will extend the query capabilities of the NDB with tools for users to search the NDB for RNA motifs using multiple criteria and to integrate search results with experimental confidence measures. We will maintain statistics on the occurrences of motifs and base pairing interactions, incorporating experimental confidence measures, and make these data available as a resource for refinement and validation tools. Each entry in the Motif Atlas will include a structural alignment of all instances of the motif to reveal sequence variants for each motif, including patterns of insertions and deletions. These data will be combined with statistical covariation data for Watson-Crick and non-Watson-Crick basepairs and statistical data for base-stacking and base- backbone interactions to develop probabilistic models for the sequence variability of each modular RNA 3D motif. These models will be used to deploy a web-based tool for users to find the 3D motif from the Motif Atlas which best matches the sequences of hairpin, internal, or junction loops that they submit. PUBLIC HEALTH RELEVANCE: Recent work shows that most of the human genome is transcribed, most of the produced RNA is non-protein coding, and a large fraction of it is critical for human reproduction, growth, and development. This proposal aims to make the growing body of experimental three-dimensional (3D) RNA structure data more useful to the biomedical research community by providing improved methods to integrate 3D RNA structure with sequence and other experimental data.

描述（由申请人提供）：我们建议通过提供改进的方法将3D RNA结构与序列和其他实验数据整合在一起，使实验三维（3D）RNA结构数据的不断增长对生物医学研究人员更有用。该项目中开发的新注释工具和服务将集成到核酸数据库（NDB）中，该数据库将为传播项目结果提供一个平台。在预期的好处中，有更好的方法是1）从序列中预测功能性RNA基序的3D结构，2）搜索基因组中的非编码RNA基因，以及3）改善同源RNA序列的比对。我们将注意力集中在复发的模块化RNA 3D基序上，这些基序发生在各种结构化的RNA分子中，并使RNA具有独特的3D形状。这包括发夹循环，内部环，接线环和第三纪相互作用图案。我们将开发系统的方法来识别，分类和命名经常性的RNA 3D图案，并定义搜索标准，以可靠地在3D结构中可靠地找到每个图案的实例。将建立一个注释程序，以便在新的结构中迅速确定新图案，并与RNA本体论财团的其他成员合作进行审查。所有实验RNA 3D结构都将用图案列表注释。将创建一个主题地图集，以在用户可用的结构中提供有关3D图案实例的信息。这个包含图案注释的新图集将添加到核酸数据库（NDB）中，核酸数据库（NDB）是一种含有含有大分子核酸的结构和功能注释的Web资源。将开发一个更新过程，以便随着新的RNA结构在PDB档案中可用时，将自动添加到NDB中的图案数据和Atlas条目。我们将使用多个标准将NDB的查询功能扩展到NDB的查询功能，以供用户搜索RNA图案，并将搜索结果与实验性置信度度量相结合。我们将维护有关基序和基础配对相互作用的发生，结合实验性置信度量的统计信息，并使这些数据作为改进和验证工具的资源可用。主题地图集中的每个条目都将包括图序的所有实例的结构对齐，以揭示每个基序的序列变体，包括插入和缺失的模式。这些数据将与Watson-Crick和Non-Watson-Crick Basepairs的统计协方差数据以及用于基础堆叠和基本骨架相互作用的统计数据，以开发每个模块化RNA 3D基序的序列变异性的概率模型。这些模型将用于部署基于Web的工具，以供用户从主题地图集中找到3D图案，该图案最能匹配他们提交的发夹，内部或交界器循环的序列。 公共卫生相关性：最近的工作表明，大多数人类基因组都是转录的，大多数生产的RNA都是非蛋白质编码，其中很大一部分对于人类繁殖，生长和发展至关重要。该建议旨在通过提供改进的方法将3D RNA结构与序列和其他实验数据相结合，使实验三维（3D）RNA结构数据的不断增长对生物医学研究界更有用。