BIOFORMATICS CORE

I.执行摘要 在布鲁斯阿罗诺博士的领导下，核心提供了创新的生物信息学服务，培训和与中心研究人员的合作，他们专注于了解消化系统功能和疾病的遗传基础。随着从消化系统疾病研究发展核心中心到Silvio O。康特DDRCC -当地称为辛辛那提消化健康中心（DHC）-核心支持在儿科消化疾病的转化研究的强烈关注。核心教师是生物医学信息学部门的成员-国家的最先进的计算基础设施和生物信息学研究和培训的中心为辛辛那提儿童研究基金会（CCRF）的家。 Core为使用基因表达微阵列、NexGen测序、RT-PCR、基于微阵列的SNP全基因组关联分析、基于Luminex和MALDI-TOF质谱等技术的蛋白质定量以及用于表征重要结构域和残基的蛋白质结构预测等技术的研究提供数据处理、分析和结果解释支持。蛋白质-蛋白质和蛋白质-药物相互作用。为此，生物信息学核心使用了一系列由生物医学信息学部门内的基础设施专家进行物理管理的资源。DHC研究人员可以直接获得核心服务，并获得个性化的支持，并针对其项目的需求，以优化知识的收益，不仅来自他们自己的遗传和基因组学数据，还来自其他多个内部和外部研究数据。通过在概念阶段提供核心咨询服务;在选择遗传学和基因组学平台期间;通过严格的质量控制评估;以及通过全面的数据挖掘，结果解释;讨论适当的验证，实验外推和出版物，调查结果也得到了改善。核心服务于DHC所有四个重点领域项目的研究需求：1）慢性肝病，2）炎症和腹泻疾病，3）肥胖和消化系统，以及4）发育和消化系统疾病。举几个例子，生物信息学核心支持的研究已经对胆道闭锁相关组织损伤和疾病表型、炎症性肠病、嗜酸性食管炎（EE）、和非酒精性脂肪性肝病-所有这些都是发病机制复杂的疾病，是儿童发病率和死亡率很高的原因，并且还为探索体内和体外胃肠干细胞和祖细胞形成和功能的基础发育生物学和翻译含义的研究提供了重要贡献。为了增强DHC研究人员的能力，核心还定期通过实践研讨会赞助生物信息学培训，这些研讨会订阅量很大，并导致积极的参与和合作。 核心领导层在加强DHC调查员研究的目标方面一直具有创新性。满足DHC项目的需求一直是独立资助的项目背后的驱动力，这些项目开发了新的计算工具来分析和推断疾病的关键基因和机制，例如GATACA，Toppgene和Toppcluster，这是一套整合工具，用于聚合，挖掘和可视化基因，途径和疾病表型的知识。这些工具的应用为DHC研究人员使用基因组技术的项目提供了令人兴奋的增强。将DHC研究者的数据与其他广泛的可用数据（如来自NCBI GEO的数据）相结合，导致了消化组数据库的开发，其目的是使DHC研究者能够进行数据分析和挖掘，以形成新的假设和对消化系统发育和疾病的理解。与基因和蛋白质表达核心合作，并得到CCRF的实质性承诺，该核心现已实施了丰富的集成工具，用于分析下一代测序衍生数据，包括外显子组测序，RNA-seq和ChIP-seq，这些工具已被DHC研究人员用于EE，IBD和干细胞相关项目。因此，本摘要强调了一个动态的生物信息学核心，为DHC研究人员提供最先进的服务，作为合作和创新的枢纽，并继续发展以支持研究人员使用先进的遗传和基因组技术，以促进对人类健康至关重要的消化系统疾病的新发现。

I. EXECUTIVE SUMMARY The Core, under the leadership of Dr. Bruce Aronow, has provided innovative bioinformatics service, training, and collaboration with Center investigators who focus on understanding the genetic basis of digestive system functions and diseases. With the evolution from a Digestive Disease Research Development Core Center to a Silvio O. Conte DDRCC - locally known as the Cincinnati Digestive Health Center (DHC) - the Core has supported a strong focus on translational research in pediatric digestive disease. Core faculty are members of the Division of Biomedical Informatics - the home of state-of-the-art computational infrastructure and a hub of bioinformatics research and training for the Cincinnati Children's Research Foundation (CCRF). The Core provides support for data processing, analysis, and results interpretation for research studies that use technologies that include gene expression microarrays, NexGen sequencing, RT-PCR, microarray-based SNP genome-wide association analysis, protein quantification based on technologies including Luminex and MALDI-TOF mass-spectrometry, and also protein structure prediction for the characterization of significant domains and residues, protein-protein and protein-drug interactions. To do this, the Bioinformatics Core uses an array of resources that are physically managed by infrastructure specialists within the Division of Biomedical Informatics. DHC investigators have direct access to Core services, and they receive support that is personalized and directed to the needs of their projects so as to optimize gains in knowledge from not only their own genetic and genomics data but also as leveraged by multiple other internal and external studies data. Investigative outcomes have also been improved by making Core consultative services available at concept stages; during selection of genetics and genomics platforms; by stringent quality control assessment; and by comprehensive data mining, results interpretation; discussion of appropriate validation, experimental extrapolation, and publication. The Core serves research needs of projects in all four focus areas of the DHC: 1) Chronic Liver Diseases, 2) Inflammatory and Diarrheal Diseases, 3) Obesity and the digestive system, and 4) Development and digestive diseases. To cite a few examples, Bioinformatics Core-enabled studies have generated new insight into the molecular basis and mechanisms of biliary atresia-associated tissue injury and disease phenotypes, inflammatory bowel disease, eosinophilic esophagitis (EE), and nonalcoholic fatty liver disease - all of which are diseases of complex pathogenesis and causes of substantial morbidity and mortality in children - and has also provided important contributions into studies probing the basic developmental biology and translational implications of gastrointestinal stem and progenitor cell formation and function in vivo and in vitro. To empower DHC investigators, the Core also regularly sponsors bioinformatics training via hands-on workshops that are well-subscribed and lead to vigorous engagement and collaboration. The Core leadership has been innovative in their goal to enhance DHC investigators' studies. Meeting the needs of DHC projects has been a driving force behind separately-funded projects that developed novel computational tools to analyze and infer critical genes and mechanisms responsible for diseases, such as GATACA, Toppgene, and Toppcluster, an integrative suite of tools for aggregating, mining and visualizing knowledge of genes, pathways, and disease phenotypes. Application of these tools has provided exciting enhancements to projects by DHC investigators that use genomic technologies. Combining DHC investigators data with extensive other available data such as from the NCBI GEO has led to the development of the Digestome Database whose aim is to enable DHC investigators to perform data analysis and mining to form new hypotheses and understanding of digestive system development and diseases. Working with the Gene and Protein Expression Core, and with a substantial commitment from CCRF, the Core has now implemented rich integrated tools for the analysis of next generation sequencing-derived data including exome sequencing, RNA-seq, and ChIP-seq, and these are already in use by DHC investigators in EE, IBD, and stem cell-related projects. Thus, this summary underscores a dynamic Bioinformatics Core that provides state-of-the-art service to DHC investigators, acts as a nidus of collaboration and innovation, and continues to evolve to support investigators' use of advanced genetic and genomic technologies to facilitate new discoveries in digestive disease critical for human health.