Informatics Infrastructure and Bioinformatics Analysis

该计划项目将涉及高通量实验，包括全基因组测序（WGS）、 细胞群 RNA 序列分析 (RNA-seq)、扰动 RNA 分析 (Perturb-seq) 和 CRISPR 屏幕。这些研究将产生大量数据，需要安全、可靠的存储和 计算分析。来自人类研究参与者的数据需要合适的数据安全级别 因为他们敏感的天性。安全且充足的计算和信息资源对于 促进所有项目的高效、一致和可重复的分析。存储程序中的所有数据 项目集中支持数据来源跟踪、数据共享和集成。共享计算支持 一致的分析管道，由单一资源负责维护数据库的当前版本 和软件。进行常规分析的生物信息学专家将使每个项目的研究人员能够 专注于新颖的研究工作。我们计划支持三个项目组成部分和其他三个项目 具有以下具体目标的核心： 目标 1. 提供信息学基础设施以实现可重复且安全的数据分析。核心B将 提供安全可靠的信息学基础设施，以支持项目的基础数据分析。一个 计算环境的关键组成部分将是具有足够计算周期和内存的服务器 项目的常规分析和新颖的研究活动。这个安全的环境将包括在线 所有原始和处理后的项目数据和分析代码的磁盘存储。该核心将实现一个精心设计的 备份系统包括项目数据的定期现场和异地备份。软件包及必备 将部署公共和许可数据库并保持最新状态。整个计算环境将是 由现代防火墙保护，系统通过 VPN 访问。系统管理员将维护 计算系统，包括备份，并将支持合作机构的用户。 目标 2：对每个项目进行常规生物信息学分析。核心 B 领域的生物信息学专家将 为基因组和转录组数据提供基本的计算分析。核心 B 的统计研究人员将 为项目 3 中的 Perturb-seq 开发创新的稳健统计方法，并为所有研究开发创新的流程。 为了对所有项目进行一致且可重复的分析，该核心将部署强大的软件 用于管理所有数据、记录其来源并跟踪所有结果的基础设施。核心将执行 WGS、转录组的预处理、质量控制、注释和其他常规分析步骤 测序、CRISPR 筛选以及基因校正特异性和效率的表征。核心B将 还有助于维护与 T 细胞缺陷相关的基因和调控区域的公共资源。核心B将 通过将所有数据集存放到适当的公众中，促进所有项目和核心的研究人员 数据库和存储库，以及所有适当的元数据。

This program project will involve high-throughput experiments, including whole genome sequencing (WGS), RNA sequence profiling on cell populations (RNA-seq), perturbation RNA profiling (Perturb-seq), and CRISPR screens. These studies will generate substantial quantities of data requiring secure, reliable storage and computational analysis. Data derived from human research participants require a data security level suitable for their sensitive nature. Secure and sufficient computational and information resources are crucial for facilitating efficient, consistent, and reproducible analyses for all projects. Storing all data from the program project centrally enables data provenance tracking, data sharing, and integration. Shared computing supports consistent analysis pipelines, with a single resource responsible for maintaining current versions of databases and software. A bioinformatics specialist performing routine analyses will allow researchers in each project to focus on novel research endeavors. We plan to support the three project components and the three other cores with the following specific aims: Aim 1. Provide informatics infrastructure to enable reproducible and secure data analyses. Core B will provide a secure and reliable informatics infrastructure to support foundational data analyses for the projects. A key component of the computing environment will be a server with sufficient compute cycles and memory for both routine analyses and novel research activities of the projects. This secure environment will include online disk storage for all raw and processed project data and analysis code. This core will implement a well-designed backup system including regular onsite and offsite backup of project data. Software packages and necessary public and licensed databases will be deployed and kept current. The entire compute environment will be secured by a modern firewall, with systems accessed via VPN. A system administrator will maintain the computing system, including backup, and will support users from the collaborating institutes. Aim 2: Perform routine bioinformatics analyses for each Project. A bioinformatics specialist in Core B will provide basic computational analyses for genome and transcriptome data. Statistical researchers in Core B will develop innovative robust statistical methods for Perturb-seq in Project 3, and creative pipelines for all studies. To enable consistent and reproducible analyses for all projects, this core will deploy a robust software infrastructure to manage all data, record its provenance, and track all results. The core will perform preprocessing, quality control, annotation, and other routine analysis steps for WGS, transcriptome sequencing, CRISPR screens, and characterization of specificity and efficiency of gene correction. Core B will also help maintain a public resource of genes and regulatory regions related to T cell deficiencies. Core B will facilitate researchers in all projects and cores with deposition of all datasets into the appropriate public databases and repositories, with all appropriate metadata.