Core B: Advanced Bioinformatics Core

核心 B：高级生物信息学核心

基本信息

批准号：
10006186
负责人：
KATHERINE S. POLLARD
金额：
$ 32.13万
依托单位：
J. DAVID GLADSTONE INSTITUTES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10006186
关键词：
ATAC-seq Address Affinity Chromatography Animal Model Automobile Driving Benchmarking Bioinformatics Biological Assay Cardiac Cardiac development Cell model ChIP-seq Chromatin Collaborations Complex Computer software Computing Methodologies Congenital Heart Defects Data Development Dissection Emerging Technologies Etiology GATA4 gene Gene Expression Gene Expression Regulation Genes Genetic Transcription Genome engineering Genomics Goals Heart Diseases In Vitro Investigation Lead Light Mass Spectrum Analysis Measures Methods Modeling Molecular Mutate Mutation Nuclear Pore Pathway Analysis Pathway interactions Phenotype Pore Proteins Post-Translational Protein Processing Program Research Project Grants Proteins Proteomics Regulator Genes Research Role Signal Transduction Statistical Methods Techniques Testing Translating Update Visualization base cardiogenesis chromatin remodeling combinatorial data integration data tools design disease phenotype diverse data experience experimental study genetic regulatory protein genome editing genomic data improved in vivo Model innovation insight machine learning method molecular phenotype myocardin novel open source protein function single-cell RNA sequencing statistics success tool transcription factor

项目摘要

PROJECT SUMMARY/ABSTRACT CORE B – ADVANCED BIOINFORMATICS CORE The Advanced Bioinformatics Core will provide innovative and collaborative computational support for all three Projects, in close partnership with the Advanced Proteomics and Genome Editing Cores. We have several decades of experience in developing statistics and bioinformatics methods for genomics and proteomics, including open source software for analysis and visualization. For nearly 10 years, we have been working closely with the Srivastava, Bruneau, and Black labs to dissect cardiac regulatory mechanisms using the latest tools for data quantification and integrative analysis. These investigations identified several key cardiac transcription factors and chromatin-remodeling proteins that can alter cardiac development and cause CHDs when mutated. Yet we do not fully understand the mechanisms through which these regulatory proteins function. It is clear from our preliminary studies that mutations alter their subcellular localization, protein interactions, and genomic occupancy. New techniques in proteomics (e.g., APEX-MS) and genomics (single- cell RNA-seq) promise to shed light on how these effects translate into disease phenotypes through altered gene regulatory networks. But there are major challenges quantifying and jointly analyzing these diverse data types. The objective of the Advanced Bioinformatics Core is to rule out chance, bias and confounding in the data from Projects 1–3, using state-of-art analyses tools when available and developing new techniques where needed. Our rigorous statistical approach will enable the Core to integrate data within and across projects to decode novel mechanisms of CHD etiology that would otherwise be missed.

项目摘要/摘要核心B - 高级生物信息学核心先进的生物信息学核心将为所有人提供创新和协作的计算支持与先进的蛋白质组学和基因组编辑核心密切合作的三个项目。我们有在开发基因组学和生物信息学方法和生物信息学方法方面的经验数十年蛋白质组学，包括用于分析和可视化的开源软件。近十年来，我们一直在与Srivastava，Bruneau和Black Labs紧密合作，使用心脏调节机制进行剖析数据量化和集成分析的最新工具。这些调查确定了几个关键心脏转录因子和染色质复制蛋白可以改变心脏发育并导致突变时的CHD。但是，我们不完全了解这些调节蛋白的机制功能。从我们的初步研究可以明显看出，突变会改变其亚细胞定位，蛋白质相互作用和基因组占用率。蛋白质组学（例如，Apex-MS）和基因组学（单一）的新技术细胞RNA-seq）有望通过改变这些影响如何转化为疾病表型基因调节网络。但是，存在量化和共同分析这些不同数据的主要挑战类型。高级生物信息学核心的目的是排除机会，偏见和混淆项目1-3的数据，使用最先进的分析工具，并开发新技术需要的地方。我们严格的统计方法将使核心能够整合在内部和跨越的数据解释冠心病病因的新型机制的项目，这些机制将被遗漏。