Core C: Biostatistics and Bioinformatics Core

项目总结 这项拟议的U19计划项目(PPG)的主要目的是全面识别男性 骨质疏松症危险基因及其功能。这项PPG申请将进行多学科/跨学科的 收敛/整合分析，以研究和整合多水平组学之间的串扰/相互作用 来自三个单独的组件项目。该计划项目涉及广泛的数据管理和 复杂的分析。这样的分析需要有机地同时考虑来自多个组件的数据 项目，并需要强大和创新的综合分析方法。因此，有必要设置 建立/维护生物统计和生物信息学核心(BBC)，专注于现有和发展的重新用途 以及新的综合分析方法的应用。 BBC的主要目标是作为实验设计改进的骨干支持资源， 数据质量控制、管理、集成、分析和解释，并作为促进数据的增效剂 以及PPG中个别项目/核心的信息交流和协作。 基于核心成员在多组学数据方面的密切和长期合作以及丰富的经验 分析认为，BBC将通过以下具体目标提供不可或缺的服务： 1)为数据管理提供高效的支持和服务，包括高质量的数据输入和 管理数据库实施和维护、数据质量控制、安全、监控、共享等。 2)为广泛的生物统计学、生物信息学和综合分析提供强有力的支持和支持。 BBC与PPG项目调查人员密切合作，将支持单级组学数据分析和 对多水平的组学数据进行综合分析。特别是，BBC将开创一种复杂的综合 分析策略。这一高度创新的策略将通过锚定基因来连接DNA/miRNA/甲基化数据- 构建统一的功能多组学模块，并将其用于功能基因 单位与疾病的关联分析。 3)评估、验证和应用新的、稳健的和强大的综合分析方法 识别/表征复杂疾病的(表观-)基因和变异。新的方法将被开发出来 (主要是在最近资助的R01)，在严格的统计框架下，并将其特征和纳入- 组学串扰/相互作用，以及先前的生物学信息，用于研究 多组学数据与疾病。这些创新方法将被应用于多元组学并进行实证检验 从这个PPG获得的数据。 核心提供的服务将被所有其他PPG项目和核心使用。总体而言，BBC将是 高效、有能力和强大地为所有PPG项目服务，特别是这个PPG的总体目标是 打算综合各个项目的成果。

PROJECT SUMMARY The main purpose of this proposed U19 program project (PPG) is to comprehensively identify male osteoporosis risk genes and their functions. This PPG application will conduct multi-/inter-disciplinary convergence/integration analyses to study and integrate the crosstalk/interaction among multi-level omics obtained from the three individual component projects. The program project involves extensive data management and complex analyses. Such analyses require organic and simultaneous consideration of data from multiple component projects, and demand powerful and innovative integrative analysis methodology. Thus, it is necessary to set up/maintain a Biostatistics and Bioinformatics Core (BBC), focusing on the repurpose of existing, and development and application of novel, integrative analysis approaches. The main Objective of the BBC is to serve as a backbone support resource for experimental design refinement, data quality control, management, integration, analyses and interpretation, and serve as a synergizer to foster data and information exchange and collaboration for individual projects/cores in the PPG. Built upon the Core members’ close and long-time collaboration and extensive experience in multi-omics data analyses, this BBC will provide indispensable services through the following Specific Aims: 1) To deliver efficient support and services for data management, including high quality data entry and management database implementation and maintenance, data quality control, safety, monitoring, sharing, etc. 2) To provide strong support for and to conduct extensive biostatistics, bioinformatics, and integrative analyses. Closely working with the PPG project investigators, the BBC will support both single-level omics data analyses and perform integrative analyses of multi-level omics data. Particularly, the BBC will pioneer a sophisticated integrative analysis strategy. This highly innovative strategy will link DNA/miRNA/methylation data through anchoring on gene- based mRNA hubs for constructing unified function multi-omics modules, which will then be used in functional gene unit and disease association analyses. 3) To evaluate, validate, and apply novel, robust and powerful integrative analysis methods for identifying/characterizing (epi-)genes and variants for complex diseases. The novel methods will be developed (mainly in a recently funded R01) under rigorous statistical frameworks, and characterize and incorporate among- omics crosstalk/interactions, along with prior biological information, for studying the causal relationship between multi-omics data and diseases. The innovative methods will be applied to and empirically tested on the multi-omics data obtained from this PPG. The services provided by the Core will be used by all other PPG projects and cores. Overall, the BBC will be efficient, capable and powerful to serve all the PPG projects, and in particular the overall goal of this PPG that intends to integrate the individual project results.