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Dissecting epitranscriptomic signal from complex tissues

剖析复杂组织的表观转录组信号

基本信息

批准号：
10677011
负责人：
Zhaohui Qin
金额：
$ 32.89万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10677011
关键词：
Basic Science Biological Biological Markers Biological Process Brain Brain region Cells ChIP-seq Characteristics Clinical Clinical Research Communities Complex Computer software DNA Methylation Data Data Analyses Data Analytics Detection Development Disease Epigenetic Process Face Foundations Gene Expression Gene Expression Regulation Genes Genetic Genetic Transcription Genome Genomic Segment Genomics Heterogeneity Immunoprecipitation Individual Joints Measurement Messenger RNA Methodology Methods Methylation Modeling Modification Molecular Morphologic artifacts Names Play Post-Transcriptional Regulation Preparation Procedures RNA RNA immunoprecipitation sequencing RNA methylation Regulation Research Ribonucleosides Role Sampling Scientist Series Signal Transduction Site Software Tools Source Statistical Methods Statistical Models Structure Technology Tissue Sample Tissues Variant bisulfite sequencing cell type complex data computerized tools crosslink crosslinking and immunoprecipitation sequencing data modeling epigenetic regulation epigenomics epitranscriptomics experience high throughput technology histone modification human disease improved infancy interest nervous system disorder neurodevelopment neuropsychiatric disorder new technology novel open source posttranscriptional research and development ribosome profiling software development therapeutic target tool transcriptome transcriptome sequencing

项目摘要

Title: Dissecting epitranscriptomic signal from complex tissues PROJECT SUMMARY: “RNA epigenetics” or “epitranscriptomics” has emerged in recent years as an exciting and active research field to study post-transcriptional regulation of gene expressions. The RNA modifications play important roles in gene expression regulation, and are involved in neurodevelopment and a number of neurological diseases. Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) is a newly developed technology for transcriptome-wise profiling of the RNA epigenetic modifications. MeRIP-seq leads to an expansion of applications in both basic and clinical research, but faces a number of challenges in analysis with its unique data characteristics, including 1) the presence of technical artifacts due to sequence content and sample preparation procedures unique to MeRIP; 2) lack of appropriate methods for identification and comparison of RNA methylated regions; and 3) lack of methods to account for the heterogeneity of tissue samples. In this proposal, we will address these challenges and develop a series of novel statistical methods for MeRIP-seq data preprocessing and analyses. They include a data normalization procedure to remove technical bias, accurate and efficient methods for RNA methylation site detection and comparison, and signal deconvolution methods to draw cell type specific inferences based on data from tissue samples. All methods developed in this project will be implemented and released as free, open source software to benefit the epigenomics research community, including basic scientists working on genetics, epigenetics, gene regulation and cell development, as well as clinicians looking for disease biomarkers.

标题：从复杂组织中解剖表观转录信号项目总结： “rna表观遗传学”或“表观转录组学”是近年来出现的一项令人兴奋和活跃的研究。研究转录后基因表达调控的领域。RNA的修饰起着重要的作用在基因表达调控中，并参与神经发育和许多神经疾病。甲基化RNA免疫沉淀测序(MERIP-SEQ)是近年来发展起来的一项新技术 RNA表观遗传修饰的转录组分析。MERIP-SEQ导致在基础和临床研究中的应用，但在分析方面面临着许多挑战，因为其独特的数据特征，包括1)由于序列内容和样本而产生的技术人工产物 MERIP特有的准备程序；2)缺乏适当的方法来鉴定和比较 RNA甲基化区域；以及3)缺乏解释组织样本异质性的方法。在这项提案中，我们将应对这些挑战，并开发一系列新的统计方法 MERIP-SEQ数据的预处理和分析。它们包括要移除的数据标准化过程技术偏差、准确高效的RNA甲基化位点检测和比较方法以及信号基于组织样本数据得出细胞类型特异性推断的去卷积方法。所有方法在此项目中开发的软件将作为免费、开放源码软件实施和发布，以使表观基因组学研究社区，包括从事遗传学、表观遗传学、基因调节和细胞发育，以及临床医生寻找疾病生物标记物。