Core B. Genomics and Bioinformatics Core

摘要-核心B(基因组学核心) 核心B(基因组核心)将为艰难梭状芽胞杆菌基因组序列的mVACS团队提供关键支持 分析、抗原设计、微生物组序列分析、常规统计分析和高含量数据 管理层。CORE B将使用先进的基于基因组学的方法来量化艰难梭菌的基因组组成 和遗传变异，并将这些与结果联系起来。核心B将支持对蛋白质结构的分析 允许以mRNAs的形式表达折叠良好的结构域。核心B将描述DNA倒置系统和其他 可能影响疫苗效力的DNA修饰和基因活性改变的机制。核心B将 也对从接种疫苗和免疫缺陷的肠道中分离的艰难梭菌进行转录图谱分析 评估艰难梭菌在体内对有效和无效免疫反应的反应。的目标是 核心B是：(1)艰难梭菌基因组学，以确定改良的mRNA疫苗的最佳靶点。长读短读 与我们之前的工作一样，读取的数据将被合并以生成完整的程序集。基因内容将是 计数并与临床结果进行比较。(2)评价C. 艰难梭菌疫苗靶标。艰难梭菌分离株编码其表面蛋白有相当大的变异。 此外，DNA倒置系统编码影响表面蛋白和转录因子的开关， 导致了广泛的种群异质性。因此，这一目标将对相关蛋白质进行深入评估 作为修饰的信使核糖核酸疫苗靶点，指导抗原设计。(3)转录图谱和微生物组 用于机械性调查的排序。项目1-3和临床核心将产生小鼠和人类 与艰难梭菌感染成功或失败反应相关的粪便样本；核心B将量化 艰难梭菌阳性标本的微生物群组成及变转录分析。这个核心 将监督序列的获取和分析是这些研究的支持。(4)数据管理和归档。 核心C将与核心A合作进行标准统计分析，并将归档和管理各种数据类型 由U19团队生成。

SUMMARY- CORE B (GENOMICS CORE) Core B (Genomics Core) will provide key support to the mVACS team in Clostridioides difficile genome sequence analysis, antigen design, microbiome sequence analysis, routine statistical analysis, and high content data management. Core B will use advanced genomics-based methods to quantify C. difficile genome composition and genetic variation, and associate these with outcomes. Core B will support analysis of protein structure to allow expression of well-folded domains as mRNAs. Core B will characterize DNA inversion systems and other mechanisms of DNA modification and alterations in gene activity that may impact vaccine efficacy. Core B will also carry out transcriptional profiling on C. difficile isolated from the intestine of vaccinated and immunodeficient mice, to assess how C. difficile responds in vivo to effective and ineffective immune responses. The Aims of Core B are: (1) C. difficile genomics to identify optimal targets for modified mRNA vaccines. Long read and short read data will be merged to generate complete assemblies, as in our previous work. Gene content will be enumerated and compared with clinical outcomes. (2) To assess variation in sequence and abundance of C. difficile vaccine targets. C. difficile isolates are known to encode considerable variation in their surface proteins. In addition, DNA inversion systems encode on-off switches affecting surface proteins and transcription factors, resulting in extensive population heterogeneity. This Aim will thus carry out deep assessment of proteins relevant as modified mRNA vaccine targets, and guide antigen design. (3) Transcriptional profiling and microbiome sequencing for mechanistic investigation. Projects 1-3 and the Clinical Core will generate murine and human fecal samples associated with successful or unsuccessful responses to C. difficile infection; Core B will quantify microbiome composition and metatranscriptomic analysis of C. difficile positive samples by RNA-seq. This core will oversee sequence acquisition and analysis is support of these studies. (4) Data management and archiving. Core C will work with Core A for standard statistical analysis and will archive and manage the diverse data types generated by the U19 team.