Core B: Molecular/Analytic Core

摘要 正在开发新的方法来最大限度地集成来自使用以下方法生成的数据的信息 “组学”技术，以揭示参与疾病发病机制的途径。在这个项目中，我们将 通过完美集成的项目和核心，利用最先进的分子和分析工具 更好地了解生物过程是如何在分子水平上定义的，它们如何被破坏以 导致非综合征性冠状颅缝早闭，以及我们如何评估其风险并进行干预以预防这种情况 先天缺陷。分子/分析核心B的目标是生成高质量的基因组和成像数据 为所有三个项目提供分析支持，以便对 颅缝融合网络。分子/分析核心将完成五项主要任务：1)生成和质量- 控制项目II和III使用的高通量和中通量遗传和基因组数据；2)生成 来自术前计算机断层扫描(CT)扫描的可分析形态测量颅面数据；3) 将从参与部位获得的临床信息与成像和遗传/基因组数据相结合，并 组织它们，使其满足不同项目的需求，4)提供一般性和专业性 对项目一和项目二的统计支助，以及5)促进选择所观察到的最高遗传信号 在颅骨融合症网络内的所有项目中进行复制研究。DNA样本将会是 使用Illumina Human OmniExpressExome高通量基因分型芯片进行处理和分析， 整个外显子组测序和中通量基因分型，用于DNA核心的复制研究，网址为 位于西奈山的伊坎医学院。将对CT图像进行处理以生成头面部测量数据 以及用于关联性研究和选择最具信息量的颅缝早闭严重程度评分 用于测序的个体。基因组和成像数据将受到质量控制，并与表型相关联 从参与站点获得的数据。分子/分析核心还将促进生物信息学和 与每个项目相关的统计分析，包括基因表达分析、罕见变异分析、 全基因组关联研究、基于途径的分析和复制研究通过产生适当的 数据集格式化和传播每个项目取得的成果。此外，分子/分析核心 将负责跨项目和核心以及数据集的数据存储和集成 为将来的数据存储和共享做好准备。

ABSTRACT New approaches are being developed to maximally integrate information from the data generated using "omics" technologies to uncover pathways involved in disease pathogenesis. In this program project, we will take advantage of state-of-the-art molecular and analytic tools through well-integrated Projects and Cores to better understand how biological processes are defined at the molecular level, how they can be disrupted to cause nonsyndromic coronal craniosynostosis, and how we can assess the risk of and intervene to prevent this birth defect. Molecular/Analytic Core B objective is to generate high quality genomic and imaging data and provide analytic support for all three Projects to allow comprehensive integrative analyses for the Craniosynostosis Network. The Molecular/Analytic Core will fulfill five major tasks: 1) to generate and quality- control high- and medium throughput genetic and genomic data to be used by Projects II and III; 2) to generate analyzable morphometric craniofacial data from pre-operational computer tomography (CT) scans; 3) to integrate clinical information obtained from the participating sites with imaging and genetic/genomic data and organize them so that they meet the needs of different Projects, 4) to provide general and specialized statistical support to Project I and Project II, and 5) to facilitate the selection of the top genetic signals observed across all Projects within the Craniosynostosis Network for the replication study. DNA samples will be processed and analyzed using the Illumina HumanOmniExpressExome high throughput genotyping chip, whole exome sequencing, and medium throughput genotyping for the replication studies in the DNA core at Icahn School of Medicine at Mount Sinai. CT images will be processed to generate craniofacial measurements and craniosynostosis severity scores to be used for association studies and to select most informative individuals for sequencing. Genomic and imaging data will be quality-controlled and linked with the phenotype data obtained from the participating sites. The Molecular/Analytic Core will also facilitate bioinformatics and statistical analyses pertinent to each project, including gene expression analysis, rare variant analysis, genome-wide association studies, pathway-based analysis, and replication studies by generating appropriate dataset formats and disseminating results obtained by each project. In addition, the Molecular/Analytic Core will be responsible for data storage and integration across the Projects and Cores, as well as dataset preparation for future data deposition and sharing.