Core B: Advanced Bioinformatics Core

核心 B：高级生物信息学核心

基本信息

批准号：
10245027
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/10245027
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.

项目概要/摘要核心 B – 高级生物信息学核心高级生物信息学核心将为所有人提供创新和协作计算支持我们与高级蛋白质组学和基因组编辑核心密切合作，开展了三个项目。在开发基因组学统计和生物信息学方法方面拥有数十年的经验近 10 年来，我们一直致力于蛋白质组学，包括用于分析和可视化的开源软件。与 Srivastava、Bruneau 和 Black 实验室密切合作，利用这些调查确定了几个关键的数据量化和综合分析工具。心脏转录因子和染色质重塑蛋白可以改变心脏发育并导致然而，我们还不完全了解这些调节蛋白发生突变的机制。从我们的初步研究可以清楚地看出，突变改变了它们的亚细胞定位，即蛋白质。蛋白质组学（例如 APEX-MS）和基因组学（单- 细胞 RNA-seq）有望揭示这些效应如何转化为疾病表型但量化和联合分析这些不同的数据存在重大挑战。高级生物信息学核心的目标是排除机会、偏见和混杂因素。来自项目 1-3 的数据，使用可用的最先进的分析工具并开发新技术我们严格的统计方法将使核心能够在需要时整合数据。项目旨在解码冠心病病因学的新机制，否则这些机制可能会被忽视。