Novel Approaches to Mammalian MicroRNA Target Prediction

哺乳动物 MicroRNA 目标预测的新方法

• 批准号: 8218582
• 负责人: YE DING
• 金额: $ 60.62万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-18 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8218582
• 关键词: 3' Untranslated Regions; Algorithms; Apoptosis; Arts; Binding; Binding Sites; Biochemical; Bioinformatics; Biological Assay; Biological Process; Biology; Cancer cell line; Code; Cognitive; Communities; Complex; Computer software; Data; Data Analyses; Databases; Development; Dimensions; Functional RNA; Gene Expression; Gene Expression Regulation; Genes; Goals; Health; Human; Immunoprecipitation; Internet; Malignant Neoplasms; Mediating; Messenger RNA; Methodology; Methods; MicroRNAs; Molecular Biology; Mus; Ontology; Outcome; Pathway interactions; Performance; Physiology; Positioning Attribute; Proteins; RNA; RNA Degradation; RNA Sequences; Regulation; Reporter; Research; Resources; Site; Software Tools; Statistical Models; Stem Cell Development; Stem cells; Structure; Systems Biology; Testing; Therapeutic; Thermodynamics; Translational Repression; Tumor Suppressor Genes; Validation; Virus; base; computerized tools; crosslink; data modeling; human disease; improved; insight; interdisciplinary approach; novel; novel strategies; robot assistance; statistics; tool; user friendly software; virology; web services

DESCRIPTION (provided by applicant): MicroRNAs (miRNAs) are an abundant class of small non-coding RNAs that regulate messenger RNAs (mRNAs) post-transcriptionally. miRNAs induce target messenger RNA degradation or translational inhibition, predominantly through cognitive binding sites in the 3 untranslated regions (3UTRs). Accurate identification of miRNA targets is essential for the understanding of their functions. Target identification has been a major challenge for understanding this recently recognized exciting dimension of gene regulation. To this end, computational target prediction methods have proven to be valuable. However, current prediction methods suffer from a number of limitations that hinder progress. Recently, biochemical purification and high throughput deep-sequencing have become feasible. Furthermore, we have developed a high-throughput methodology to experimentally test thousands of miRNA-3UTR interactions, and have acquired mRNA/miRNA expression data on hundreds of cancer cell lines. These experimental advances have presented us the opportunity to develop state-of-the-art miRNA target prediction algorithms. In this application, we propose to adapt an interdisciplinary approach to develop novel miRNA-target prediction algorithms to overcome the limitations of current prediction algorithms. Our complementary expertise in RNA Bioinformatics and Statistics and large scale experimental testing have placed us in a unique position to pursue the following specific aims: 1) Develop a target prediction algorithm based on deep sequencing data from biochemically purified miRNA-target complexes; 2) Perform large-scale miRNA-3UTR reporter assays to derive functional miRNA-target interactions; 3) Develop algorithms and perform analyses and validation for more informative predictions on the level of miRNA-mediated regulation and miRNA-regulated pathways and networks; 4) Develop user-friendly software tools and database for distribution to the scientific community. This project will advance our understanding of miRNA-mediated gene regulation in molecular biology and systems biology, facilitate development of miRNA-based therapeutics, and in turn benefit human health. PUBLIC HEALTH RELEVANCE: Novel Approaches to Mammalian MicroRNA Target Prediction Project Relevance Accurate identification of microRNA targets is essential for understanding the diverse functions of microRNAs in gene regulation. The computational tools developed from this project will be broadly applicable to mammalian species beyond human and mouse, as well as stem cells and viruses. Thus, this project will contribute to the advancement of microRNA biology, the understanding of microRNA functions in cancer and other human diseases, and the development of microRNA-based therapeutics.

描述（由申请人提供）：microRNA（miRNA）是一类大量的小型非编码RNA，在转录后调节Messenger RNA（mRNA）。 miRNA诱导目标使者RNA降解或翻译抑制作用，主要通过3个未翻译区域的认知结合位点（3UTR）。准确鉴定miRNA靶标对于理解其功能至关重要。目标识别一直是理解这一最近公认的基因调控维度的主要挑战。为此，证明计算目标预测方法是有价值的。但是，当前的预测方法遭受了许多阻碍进步的局限性。最近，生化的纯化和高吞吐量的深层后续结构变得可行。此外，我们已经开发了一种高通量方法来实验测试数千种miRNA-3UTR相互作用，并在数百个癌细胞系上获得了mRNA/miRNA表达数据。这些实验进步使我们有机会开发最新的miRNA目标预测算法。 在此应用中，我们建议适应一种跨学科的方法来开发新颖的miRNA目标预测算法，以克服当前预测算法的局限性。我们在RNA生物信息学和统计学以及大规模实验测试方面的互补专业知识使我们处于独特的位置，以追求以下特定目的：1）基于从生化纯化的MiRNA-Target核心复合物中的深层测序数据开发目标预测算法； 2）执行大规模miRNA-3UTR报告基因测定法以得出功能miRNA-target相互作用； 3）开发算法并进行分析和验证，以对miRNA介导的调节和miRNA调节途径和网络的水平进行更有信息的预测； 4）开发用户友好的软件工具和数据库，以分发向科学界分发。该项目将促进我们对分子生物学和系统生物学中miRNA介导的基因调节的理解，促进基于miRNA的治疗剂的发展，进而使人类健康受益。 公共卫生相关性：哺乳动物microRNA目标预测项目的新方法准确鉴定microRNA目标对于理解microRNA在基因调节中的多种功能至关重要。该项目开发的计算工具将广泛适用于人类和小鼠以外的哺乳动物物种以及干细胞和病毒。因此，该项目将有助于MicroRNA生物学的发展，对癌症和其他人类疾病中microRNA功能的理解以及基于microRNA的疗法的发展。