Mapping Somatic TE-derived Transcriptional Diversity

绘制体细胞 TE 衍生的转录多样性

基本信息

批准号：
10155548
负责人：
Tracy Ann Bedrosian
金额：
$ 13.15万
依托单位：
RESEARCH INST NATIONWIDE CHILDREN'S HOSP
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10155548
关键词：
Affect Alternative Splicing Area Astrocytes Bioinformatics Biology Blood Brain Catalogs Cell Fraction Cell model Cells Characteristics Clustered Regularly Interspaced Short Palindromic Repeats Complement Complex DNA DNA Insertion Elements DNA Transposable Elements Data Set Detection Disease Electrophysiology (science)Event Gene Expression Genes Genetic Genetic Materials Genetic Transcription Genetic Variation Genome Genomics Goals Human Human Genome Individual Inherited Knowledge Lead Maps Mediating Methods Mobile Genetic Elements Modeling Molecular Morphology Mosaicism Mutation Neurons Neurosciences Operative Surgical Procedures Patients Pediatric cohort Phenotype Population Process RNA RNA Splicing Reporting Resected Site Somatic Mutation Source Technology Time Training Transcript Translational Research Variant brain cell brain tissue career cell type childhood epilepsy disorder risk experience gene expression variation genome sequencing genome-wide genomic locus human disease individual variation induced pluripotent stem cell multiple omics new technology novel population based protein expression skills transcriptome transcriptome sequencing

项目摘要

Project Summary/Abstract Nearly half of the human genome is derived from transposable elements (TEs) -- mobile genetic elements that replicate and insert copies of themselves throughout the genome. Each individual has a unique signature of TE insertions comprised of inherited germline insertions and acquired somatic insertions. This signature is a major source of genetic variation both between individuals and within an individual. TEs have the potential to alter the transcriptome in a variety of ways, but the extent of intra-individual TE-derived transcriptional diversity is unknown. Detecting the transcriptional effects of somatic transposition has historically been challenging given the rarity of each insertion event on a per cell basis. New methods are finally enabling simultaneous interrogation of genome and transcriptome from a single cell, making it possible to detect both germline polymorphic and somatic transposition events and directly probe their consequences. This proposal will leverage single cell multi- omics technology to map somatic TE-derived transcriptional and functional diversity in the brain. Understanding the functional impact of somatic TE activity will ultimately contribute to our understanding of individual variation underlying complex disease processes. The training aspect of this project will support the applicant’s career goal to lead a translational research group that investigates the functional effects of somatic variation on human disease processes. Training in single-cell genomics is essential to probe the influence of rare somatic mutations in the brain. The proposal will build upon the applicant’s previous experience with experimental biology and molecular neuroscience while supporting critical training in bioinformatics and computational genomics.

项目概要/摘要近一半的人类基因组源自转座元件（TE）——可移动的遗传元件，在整个基因组中复制并插入自己的副本每个个体都有独特的 TE 签名。这个签名是一个大个体之间和个体内部的遗传变异源都有可能改变个体的遗传变异。转录组以多种方式存在，但个体内 TE 衍生的转录多样性的程度检测体细胞转座的转录效应历来都是具有挑战性的。考虑到每个细胞的每个插入事件的稀有性，新方法最终能够实现同时询问。来自单个细胞的基因组和转录组，使得检测种系多态性和该提案将利用单细胞多细胞的体细胞转座事件并直接探讨其后果。组学技术绘制大脑中体细胞 TE 衍生的转录和功能多样性。体细胞 TE 活动的功能影响最终将有助于我们对个体差异的理解该项目的培训方面将支持申请人的职业目标。领导一个转化研究小组，研究体细胞变异对人类的功能影响单细胞基因组学培训对于探究罕见体细胞突变的影响至关重要。该提案将建立在申请人之前的实验生物学经验和分子神经科学，同时支持生物信息学和计算基因组学的关键培训。