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.

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).准确识别 miRNA 靶点对于理解其功能至关重要。目标识别一直是理解最近认识到的令人兴奋的基因调控维度的主要挑战。 To this end, computational target prediction methods have proven to be valuable.然而，当前的预测方法存在许多阻碍进展的限制。最近，生化纯化和高通量深度测序已变得可行。 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) 开发用户友好的软件工具和数据库以分发给科学界。 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.