Innovations in RNA Structure Prediction
RNA 结构预测的创新
基本信息
- 批准号:8131933
- 负责人:
- 金额:$ 32.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-25 至 2012-11-30
- 项目状态:已结题
- 来源:
- 关键词:AlgorithmsAntisense TechnologyBase PairingBiologyCatalytic RNACell physiologyCodeComputer softwareDevelopmentEvolutionFree EnergyFunctional RNAFungal GenomeGene Expression RegulationGenesGenetic CarriersGenomeGoalsGoldHealthHumanHuman GenomeImmunityIn VitroMethodsMyotonic DystrophyPeptidesPlayRNARNA InterferenceRNA Sequence AnalysisRNA SequencesRNA SplicingReactionReadingResearchResearch PersonnelRoleScanningScientistSequence AnalysisSequence HomologsStructureTestingTherapeuticWorkWritingbasecomparativegenome sequencinghuman diseaseimprovedinnovationnovelprogramsskillstool
项目摘要
DESCRIPTION (provided by applicant): RNA plays many important roles in cellular function. In the Central Dogma of Biology, RNA serves as a transient carrier of genetic information and as the adapter molecule that reads the code. RNA catalyzes reactions and serves in post-transcriptional gene regulation, development, and immunity. RNA also plays roles in human disease, including Praeder-Willi and myotonic dystrophy. Understanding and harnessing the power of RNA, e.g. with RNAi, antisense technology, or with therapeutic ribozymes, requires an understanding of the structures of these RNA sequences. The goals of this proposal are to (1) Automate comparative sequence analysis of RNA to determine RNA secondary structure using pairwise structure predictions from Dynalign, our algorithm that finds the secondary structure common to two sequences. Comparative sequence analysis is the gold standard for determining RNA secondary structure in the absence of a crystal structure, but is currently labor intensive and dependent on the skill of the scientist doing the comparison. With the discovery of new classes of non-coding RNA (ncRNA) sequences that function without coding message, there is a significant need for new tools to automate the determination of secondary structure. (2) Further develop our method using Dynalign for ncRNA discovery by writing a new software package called Dynafind. Our method for ncRNA discovery takes crudely aligned sequence as input and identifies putative ncRNAs on the basis of the folding free energy change of the common structure in the alignment. (3) Scan the human and yeast genomes for novel ncRNA genes using Dynafind. We will collaborate with our co-investigators, Dr. Eric Phizicky and Dr. Todd Lowe, to test the function of putative ncRNAs that we identify. This work has broad implications for human health. Improved tools for predicting RNA structure will help in the discovery of therapeutics that are either RNA or target RNA. The discovery of novel ncRNA in the human genome will contribute to our understanding of development and cellular physiology.
描述(申请人提供):RNA在细胞功能中扮演许多重要角色。在生物学的中心法则中,RNA充当遗传信息的瞬时载体和读取密码的适配分子。RNA催化反应,参与转录后基因调控、发育和免疫。RNA还在人类疾病中发挥作用,包括Praeder-Willi和强直性肌营养不良。理解和利用RNA的力量,例如通过RNAi、反义技术或治疗性核酶,需要了解这些RNA序列的结构。该建议的目标是(1)自动进行RNA的比较序列分析,使用来自DyAlign的成对结构预测来确定RNA的二级结构,我们的算法找到了两个序列共有的二级结构。比较序列分析是在没有晶体结构的情况下确定RNA二级结构的金标准,但目前是劳动密集型的,依赖于进行比较的科学家的技能。随着新的非编码RNA(NcRNA)序列的发现,这些序列的功能不需要编码信息,因此需要新的工具来自动确定二级结构。(2)通过编写一个新的软件包Dyafind,进一步发展了我们的方法,使用Dyign来发现ncRNA。我们的ncRNA发现方法以粗比对序列为输入,根据比对中常见结构的折叠自由能变化来识别可能的ncRNA。(3)使用DYNAFIND扫描人类和酵母基因组中新的ncRNA基因。我们将与我们的合作研究人员Eric Phizky博士和Todd Lowe博士合作,测试我们识别的假定ncRNA的功能。这项工作对人类健康具有广泛的影响。预测RNA结构的改进工具将有助于发现RNA或靶向RNA的治疗药物。人类基因组中新的ncRNA的发现将有助于我们理解发育和细胞生理学。
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Amber ff99 Force Field Predicts Relative Free Energy Changes for RNA Helix Formation.
- DOI:10.1021/ct300240k
- 发表时间:2012-07-10
- 期刊:
- 影响因子:5.5
- 作者:Spasic, Aleksandar;Serafini, John;Mathews, David H.
- 通讯作者:Mathews, David H.
Stochastic sampling of the RNA structural alignment space.
- DOI:10.1093/nar/gkp276
- 发表时间:2009-07
- 期刊:
- 影响因子:14.9
- 作者:Harmanci AO;Sharma G;Mathews DH
- 通讯作者:Mathews DH
Discovery of permuted and recently split transfer RNAs in Archaea.
- DOI:10.1186/gb-2011-12-4-r38
- 发表时间:2011
- 期刊:
- 影响因子:12.3
- 作者:Chan PP;Cozen AE;Lowe TM
- 通讯作者:Lowe TM
Automated RNA tertiary structure prediction from secondary structure and low-resolution restraints.
- DOI:10.1002/jcc.21806
- 发表时间:2011-07-30
- 期刊:
- 影响因子:3
- 作者:Seetin, Matthew G.;Mathews, David H.
- 通讯作者:Mathews, David H.
Statistical evaluation of improvement in RNA secondary structure prediction.
- DOI:10.1093/nar/gkr1081
- 发表时间:2012-02
- 期刊:
- 影响因子:14.9
- 作者:Xu Z;Almudevar A;Mathews DH
- 通讯作者:Mathews DH
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{{ truncateString('DAVID H. MATHEWS', 18)}}的其他基金
RNA Structure Modeling Using Physics and Sequence Comparison
使用物理和序列比较进行 RNA 结构建模
- 批准号:
10405399 - 财政年份:2022
- 资助金额:
$ 32.59万 - 项目类别:
RNA Structure Modeling Using Physics and Sequence Comparison
使用物理和序列比较进行 RNA 结构建模
- 批准号:
10685332 - 财政年份:2022
- 资助金额:
$ 32.59万 - 项目类别:
Automated Comparative Sequence Analysis of RNA Secondary and Tertiary Structure
RNA 二级和三级结构的自动比较序列分析
- 批准号:
10374883 - 财政年份:2019
- 资助金额:
$ 32.59万 - 项目类别:
Automated Comparative Sequence Analysis of RNA Secondary and Tertiary Structure
RNA 二级和三级结构的自动比较序列分析
- 批准号:
9903401 - 财政年份:2019
- 资助金额:
$ 32.59万 - 项目类别:
Supporting RNAstructure: Software for RNA Analysis
支持 RNAstruct:RNA 分析软件
- 批准号:
7123278 - 财政年份:2006
- 资助金额:
$ 32.59万 - 项目类别:
Supporting RNA structure: Software for RNA Analysis
支持 RNA 结构:RNA 分析软件
- 批准号:
9762909 - 财政年份:2006
- 资助金额:
$ 32.59万 - 项目类别:
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