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：
10184935
负责人：
Hao Wu
金额：
$ 34.17万
依托单位：
EMORY 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/10184935
关键词：
Address 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 base 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 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：剖析复杂组织的表观转录组信号项目概要：近年来，“RNA表观遗传学”或“表观转录组学”成为一项令人兴奋且活跃的研究 RNA修饰在研究基因表达的转录后调控领域发挥着重要作用。参与基因表达调控，并参与神经发育和许多神经系统疾病。甲基化RNA免疫沉淀测序（MeRIP-seq）是一项新开发的技术，用于 MeRIP-seq 的转录组分析导致 RNA 表观遗传修饰的扩展。在基础研究和临床研究中都有应用，但以其独特的特性在分析中面临着许多挑战数据特征，包括 1) 由于序列内容和样本而存在技术假象 MeRIP特有的制备程序；2）缺乏适当的鉴定和比较方法 RNA 甲基化区域；3) 缺乏解释组织样本异质性的方法。在本提案中，我们将解决这些挑战并开发一系列新颖的统计方法 MeRIP-seq 数据预处理和分析包括数据标准化程序以删除。技术偏差、准确有效的 RNA 甲基化位点检测和比较方法以及信号根据组织样本的数据得出细胞类型特定推论的反卷积方法所有方法。该项目中开发的产品将作为免费开源软件实施和发布，以造福于表观基因组学研究团体，包括从事遗传学、表观遗传学、基因研究的基础科学家调节和细胞发育，以及寻找疾病生物标志物。