Linking sequence and copy number variation to eye diseases by regulatory genomics

通过调控基因组学将序列和拷贝数变异与眼部疾病联系起来

基本信息

批准号：
9044785
负责人：
Peter J Park
金额：
$ 38.14万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9044785
关键词：
Adult Affect Algorithms Area Attention Binding Bioinformatics Biological Biology Cells Collection Communities Complement Complex Copy Number Polymorphism Data Data Set Databases Detection Disease Embryonic Development Encyclopedia of DNA Elements Eye Eye Development Eye diseases Galaxy Gene Expression Gene Expression Profile Gene Expression Profiling Gene Expression Regulation Genes Genetic Genetic study Genome Genomics Health Histocompatibility Testing Imagery Knowledge Laboratories Link Meta-Analysis Methods Morphologic artifacts Nucleotides Online Systems Pathway interactions Phenotype Photoreceptors Physicians Process Regulator Genes Regulatory Element Regulatory Pathway Research Resources Retina Retinal Diseases Scientist Source System Tissue-Specific Gene Expression Tissues Variant Vision Disorders base cancer genome cell type cohort epigenomics exome exome sequencing functional genomics gene discovery genetic variant genome analysis genome sequencing genome wide association study histone modification human disease improved innovation insight interest knowledge base lens personalized genomic medicine repository research study tool transcription factor user-friendly whole genome

项目摘要

DESCRIPTION (provided by applicant): We propose to develop and apply innovative bioinformatic analysis tools for studying the genomics of vision disorders, focusing on lens- and retina-related diseases. We hypothesize that integrative analysis of existing functional genomic datasets, such as profiles of gene expression, histone modification, transcription factor binding, and perturbation experiments, can greatly facilitate interpretation of sequence and copy number variants identified in genome-wide association studies (GWAS) or whole-genome/exome sequencing studies. In Aim 1, we will use available genomic datasets to construct a gene regulatory network for both the lens and the retina. In Aim 2, we will perform meta-analysis of GWAS datasets to search for copy number variants that are correlated with the phenotype, using improved methods for cross-platform analysis. In Aim 3, we will develop copy number variation detection algorithm for exome data and develop a framework for prioritization of variants using epigenomic data available from the Encyclopedia of DNA Elements (ENCODE) project. In Aim 4, we propose to integrate the variants we find with information from existing resources in an eye-disease specific variant database and exploration platform, using a customized workflow system we have already developed. Many of the proposed analyses take advantage of the tools that were developed originally for cancer genome analysis. The gene regulatory networks, improved algorithms, and integrated workflows developed in this proposal are likely to be a widely applicable resource to the eye research community.

描述（由申请人提供）：我们建议开发和应用创新的生物信息学分析工具来研究视力障碍的基因组学，重点关注与镜头和视网膜相关的疾病。我们假设对现有功能基因组数据集的综合分析，例如基因表达，组蛋白修饰，转录因子结合和扰动实验，可以极大地促进对全基因组关联研究（GWAS）（GWAS）或全基因组序列/exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exenome/Exemem序列研究中鉴定出的序列和拷贝数变体的解释。在AIM 1中，我们将使用可用的基因组数据集构建镜头和视网膜的基因调节网络。在AIM 2中，我们将使用改进的方法进行跨平台分析，对GWAS数据集的荟萃分析进行搜索与表型相关的拷贝数变体。在AIM 3中，我们将开发用于外部数据的拷贝数变化检测算法，并使用可从DNA元素百科全书（ENCODE）项目获得的表观基因组数据开发一个框架，以优先考虑变体的框架。在AIM 4中，我们建议使用我们已经开发的自定义工作流程系统将发现的变体与现有资源的信息集成在一起。许多提出的分析利用了最初用于癌症基因组分析的工具。本提案中开发的基因调节网络，改进的算法和综合工作流程可能是对眼睛研究社区的广泛适用资源。