Classification, Characterization and Database Searching of RNA Motifs

描述(由申请人提供)：本项目旨在执行与RNA本体(RNAO)的开发相关并支持其发展的具体研究任务，RNAO是开放生物医学本体(OBO)联盟的核心、正交本体，也是序列本体(SO)的伙伴。P.I.是RNA本体论联盟(ROC)的召集人，该联盟在RNA协会的赞助下开发RNAO。本体论的第一个版本(RNAO.owl)将在2009年5月的RNA学会年会上公布。通过整合与RNA 3D结构、RNA序列和RNA功能有关的不同数据库，RNAO将服务于多种RNA研究议程，包括根据序列预测RNA3D结构、同源RNA序列的多重比对、非编码RNA的基因组搜索以及用于生物传感和药物输送等不同应用的基于RNA的纳米结构的设计。这项拟议的研究应用生物信息学、计算和生物物理工具来获得关于RNA相互作用和重复的3D基序的基础数据。本项目的具体目标包括：a.1。碱基堆积：开展生物信息学统计研究和有针对性的实验研究，以探索RNA基序中堆积相互作用的碱基特异性。A.2.碱基三联体：对3D结构中的所有碱基三联体进行提取、分类和聚类，并鉴定在同源RNA分子中相应位置替换的同位异构性碱基三联体。对在3D数据库中高度过高或过低的选定碱基三元组进行QM计算，优化它们的结构，比较它们的能量学，并评估它们的结构稳定性。A.3.多螺旋连接和三级相互作用：开发算法和编写软件，从RNA3D结构中提取所有多螺旋连接和所有三级相互作用，包括假结。根据几何标准对所有基序进行聚类和分类，并扩展在线RNA 3D基序库以包括多螺旋连接和三级相互作用基序。A.4.协作环境：为RNA Ontology Consortium(ROC)的成员创建一个在线协作环境，以比较和评估建议的RNA3D基序类别和定义。A.5.SCFG/MRF模型包含堆积和碱基-磷酸盐相互作用。将碱基堆积和碱基-磷酸相互作用的评分项纳入先前开发的SCFG/MRF模型中，以测试它们仅从序列中增强识别Motif 3D结构的能力。A.6.实验研究。进行热力学研究，以评估碱基堆积、碱基配对和碱基-磷酸相互作用对重复的RNA3D基序稳定性的贡献。 与公共健康相关：RNA分子在人类细胞基因表达的所有阶段都发挥着至关重要的作用，并与许多疾病有关，包括心脏病、糖尿病和各种形式的癌症。许多RNA分子形成独特的3D结构来实现它们的功能。该提案支持开发RNA本体(RNAO)，RNAO是开放生物医学本体(OBO)联盟的核心本体，也是序列本体(SO)的伙伴，以促进与RNA 3D结构、同源序列和RNA功能有关的数据库的集成，以实现对各种RNA数据的智能数据挖掘并将其快速转化为有用的知识。

DESCRIPTION (provided by applicant): This project is designed to carry out specific research tasks relevant to and supportive of the development of the RNA Ontology (RNAO), a core, orthogonal ontology of the Open Biomedical Ontologies (OBO) Consortium and companion to the Sequence Ontology (SO). The P.I. is the convener of the RNA Ontology Consortium (ROC), which is developing RNAO under the auspices of the RNA Society. The first version of the ontology (RNAO.owl) is being presented at the RNA Society annual meeting, May 2009. By integrating diverse databases pertaining to RNA 3D structures, RNA sequences, and RNA functions, the RNAO will serve multiple RNA research agendas, including prediction of RNA 3D structures from sequence, multiple alignment of homologous RNA sequence, genome searching for non-coding RNAs, and the design of RNA-based nanostructures for diverse applications, such as biosensing and drug delivery. The proposed research applies bioinformatic, computational, and biophysical tools to obtain fundamental data on RNA interactions and recurrent 3D motifs. The specific aims of this project include: A.1. Base Stacking: To carry out bioinformatic statistical studies and targeted experimental studies to explore the base specificity of stacking interactions in RNA motifs. A.2. Base Triples: To extract, classify and cluster all base triples in 3D structures and to identify isosteric base triples that substitute at corresponding positions in homologous RNA molecules. To carry out QM calculations on selected base triples that are highly over- or under-represented in the 3D database, optimize their structures, compare their energetics and assess their structural stabilities. A.3. Multi-helix junctions and tertiary interactions: To develop algorithms and write software that will extract from RNA 3D structures all multi-helix junctions and all tertiary interactions, including pseudoknots. To cluster and classify all motifs based on geometric criteria and to extend the on-line RNA 3D Motif Library to include multi-helix junction and tertiary interaction motifs. A.4. Collaborative Environment: To create an on-line collaborative environment for members of the RNA Ontology Consortium (ROC) to compare and evaluate proposed RNA 3D Motif classes and definitions. A.5. SCFG/MRF models which incorporate stacking and base-phosphate interactions. Incorporate scoring terms for base stacking and base-phosphate interactions into the SCFG/MRF models developed previously to test their ability to enhance the identification of motif 3D structure from sequence alone. A.6. Experimental Studies. To perform thermodynamic studies to assess the contributions of base-stacking, base-pairing, and base-phosphate interactions to the stabilities of recurrent RNA 3D motifs. PUBLIC HEALTH RELEVANCE: RNA molecules play essential roles in all stages of gene expression in human cells and have been implicated in many diseases including heart disease, diabetes, and various forms of cancer. Many RNA molecules form unique 3D structures to carry out their functions. This proposal supports the development of the RNA Ontology (RNAO), a core ontology of the Open Biomedical Ontologies (OBO) Consortium and companion to the Sequence Ontology (SO), to facilitate integration of databases pertaining to RNA 3D structure, homologous sequences, and RNA functions to enable intelligent data-mining of diverse RNA data and their rapid translation into useful knowledge.