Cardiovascular Development Data Resource Center (CDDRC)

项目摘要 先天性心脏病（CHD）影响美国每年出生的所有儿童的约1%。 NHLBI已经进行了大量投资，以发现冠心病的原因和结果，包括研究 在台架到摇篮（B2B）联盟中，该联盟涵盖心血管领域的基础发现科学， 发展联盟（CvDC），测序临床表现型CHD儿童的基因组， 他们的父母在儿科心脏基因组学联盟（PCGC），长期临床随访， 儿科心脏网络（PHN）的结果研究。下一代测序（NGS） 迅速加速了心血管发育和CHD遗传学和表观遗传学的发现。 CvDC和PCGC都有广泛的NGS数据集。犹他州大学的CvDC数据中心 目前作为程序化数据仓库和分发服务器，组织NGS数据集， 让他们可以在网上看到。CvDC数据集是复杂的，包含来自七个模型的NGS实验 生物物种（小鼠、斑马鱼、人类、鳄鱼、海龟、鸡、羊和青蛙）和人类。 重要的是，CvDC中的实验探索了心血管发育的分子病因学 通过几种协调的组学方法，研究全基因组转录组的变化， 表观基因组（染色质修饰因子、转录因子、DNA甲基化组和高级组织） 在心脏发育过程中和几种突变的遗传背景中。 心血管发展数据资源中心（CDDRC）将建立在创新的Mosaic 提供基于云的协作空间，用于组织、可视化和理解基因组 数据，并将分析工具指向云上任何地方的数据集。CDDRC由以下人员设计： 计算科学和生物信息学专家，与CvDC，PCGC和 PHN供非专家、基础科学家、人类遗传学家和临床医生使用。犹他州大学是 在所有三个B2B联盟中拥有领导地位的国家少数机构之一，反映了深度和 我们的专业知识的多样性和我们对跨学科合作的承诺。CDDRC将提供一个 一套云兼容工具和一组协调一致的数据集， 以前的CvDC DataHub，从当前的CvDC项目导入，并从心血管 发展和儿科CHD研究社区。CDDRC将促进动态和调查员- 与来自人类和多种模式生物的多组学数据集的交互界面， CHD的遗传和表观遗传原因的合作发现。此外，我们的计划将有 CHD遗传学和基因组学的伦理、法律的和社会影响（ELSI）教育内容，以及 CHD计算生物学的一个外展计划，针对来自代表性不足群体的学生。

PROJECT SUMMARY Congenital heart disease (CHD) affects approximately 1% of all children born per year in the United States. The NHLBI has made significant investments to discover the causes and outcomes of CHD, including research in the Bench-to-Bassinet (B2B) Consortia that spans fundamental discovery science in the Cardiovascular Development Consortium (CvDC), sequencing the genomes of clinically phenotyped children with CHD and their parents in the Pediatric Cardiac Genomics Consortium (PCGC), and long-term clinical follow-up and outcomes research in the Pediatric Heart Network (PHN). The advent of Next Generation Sequencing (NGS) has rapidly accelerated discoveries in cardiovascular development and the genetics and epigenetics of CHD. Both the CvDC and the PCGC have extensive NGS datasets. The CvDC DataHub at the University of Utah currently serves as the programmatic data warehouse and distribution server that organizes NGS datasets and makes them available online. CvDC datasets are complex, containing NGS experiments from seven ‘model organism’ species (mice, zebrafish, humans, alligator, turtle, chicken, sheep and frogs) and humans. Importantly, the experiments in the CvDC explore the molecular etiology of cardiovascular development through several coordinated -omics approaches, studying changes in the whole-genome transcriptome and in the epigenome (chromatin modifiers, transcription factors, the DNA methylome and higher-order organization of chromatin) during cardiac development and in several mutant genetic backgrounds. The Cardiovascular Development Data Resource Center (CDDRC) will be built on the innovative Mosaic platform to provide a cloud-based collaborative space for organizing, visualizing and understanding genomic data, and for pointing analytic tools to datasets housed anywhere on the cloud. The CDDRC is designed by experts in computational sciences and bioinformatics, in consultation with leaders in the CvDC, PCGC and PHN to be used by non-experts, basic scientists, human geneticists and clinicians. The University of Utah is one of a few institutions in the country that has leadership in all three B2B consortia, reflecting the depth and diversity of our expertise and our commitment to cross-disciplinary collaborations. The CDDRC will provide a suite of cloud-compatible tools and a coordinated and a harmonized set of datasets transported from the previous CvDC DataHub, imported from current CvDC projects, and recruited from the cardiovascular development and pediatric CHD research communities. The CDDRC will facilitate dynamic and investigator- interactive interfaces with multiple -omics datasets from humans and multiple model organisms, resulting in collaborative discoveries of the genetic and epigenetic causes of CHD. In addition, our program will have educational components in Ethical, Legal and Social Implications (ELSI) of CHD genetics and genomics, and an outreach program in CHD computational biology for students from underrepresented groups.