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：从复杂组织中解剖表参数信号项目摘要：近年来，“ RNA表观遗传学”或“表面翻译组学”已成为一项令人兴奋而积极的研究研究基因表达的转录后调节。 RNA修饰起着重要的作用在基因表达调节中，并参与神经发育和许多神经系统疾病。甲基化的RNA免疫沉淀测序（Merip-Seq）是一种新开发的技术 RNA表观遗传修饰的转录组分析。 Merip-seq导致在基础研究和临床研究中的应用，但在分析方面面临许多挑战数据特征，包括1）由于序列含量和样品而存在技术伪像 Merip独有的准备程序； 2）缺乏适当的识别和比较方法 RNA甲基化区域； 3）缺乏解决组织样品异质性的方法。在此提案中，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。它们包括一个数据归一化过程以删除技术偏见，RNA甲基化位点检测和比较的准确有效方法以及信号根据组织样品数据绘制细胞类型特定推断的反卷积方法。所有方法该项目中开发的将作为免费的开源软件实施并发布，以使表观基因组学研究界，包括从事遗传学，表观学，基因的基础科学家调节和细胞发育以及寻找疾病生物标志物的临床医生。