BIOFORMATICS CORE

生物信息学核心

• 批准号: 8894494
• 负责人: Bruce J Aronow
• 金额: $ 15.4万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8894494
• 关键词: Affect; Applied Research; Architecture; Area; Basic Science; Bayesian Modeling; Biliary Atresia; Binding Sites; Bioinformatics; Biological; Cells; ChIP-on-chip; ChIP-seq; Child; Childhood; Chromatin; Chromosomes; Collaborations; Complex; Computer Simulation; Computer software; Consult; Consultations; Controlled Study; Copy Number Polymorphism; CpG Islands; Custom; DNA; DNA Sequence; Data; Data Analyses; Data Set; Databases; Development; Developmental Biology; Digestive System Disorders; Disease; Disease model; Distal; Drug Interactions; Educational Activities; Educational workshop; Embryonic Development; Environment; Eosinophilic Esophagitis; Evolution; Experimental Designs; Faculty; Family; Foundations; Funding; Gastroenterology; Gene Chips; Gene Expression; Gene Expression Profile; Gene Structure; Generations; Genes; Genetic; Genome; Genomic approach; Genomics; Goals; Health; Hepatobiliary; Hepatology; High Performance Computing; Home environment; Housing; Human; Immunoprecipitation; In Vitro; Indium; Individual; Inflammatory; Inflammatory Bowel Diseases; Informatics; Injury; Internet; Knowledge; Lead; Leadership; Link; Liver diseases; Location; MALDI-TOF Mass Spectrometry; Measurement; Medicine; Messenger RNA; Methods; Methylation; MicroRNAs; Microarray Analysis; Mining; Modeling; Molecular; Morbidity - disease rate; Morphology; Names; Obesity; Online Systems; Outcome; Pathogenesis; Pathway interactions; Patients; Pattern; Population Control; Productivity; Protein Analysis; Proteins; Proteomics; Protocols documentation; Publications; Quality Control; Quantitative Genetics; Regulatory Element; Research; Research Infrastructure; Research Personnel; Research Training; Resources; Reverse Transcriptase Polymerase Chain Reaction; SNP genotyping; Sampling; Services; Specialist; Staging; Statistical Models; Stem cells; Structure; Sum; System; Systems Biology; Systems Development; Systems Integration; Techniques; Technology; Tissues; Training; Training Support; Translational Research; Validation; Variant; Work; base; bench to bedside; biological systems; biomedical informatics; chronic liver disease; computer infrastructure; computerized data processing; computerized tools; cost efficient; data mining; density; design; differential expression; direct application; disease phenotype; driving force; empowered; exome; exome sequencing; gastrointestinal; gastrointestinal system; gene function; genetic analysis; genetic pedigree; genetic selection; genome wide association study; high standard; improved; in vivo; innovation; insight; interest; meetings; member; mortality; new technology; next generation; next generation sequencing; non-alcoholic fatty liver; novel; organ growth; patient population; postnatal; promoter; protein expression; protein structure prediction; research and development; research study; software development; stem; tool; transcription factor; transcriptome sequencing; transcriptomics

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.

一、执行摘要 该核心在 Bruce Aronow 博士的领导下，提供创新的生物信息学服务、培训以及与中心研究人员的合作，这些研究人员专注于了解消化系统功能和疾病的遗传基础。随着消化疾病研究开发核心中心发展为 Silvio O. Conte DDRCC（当地称为辛辛那提消化健康中心 (DHC)），该核心支持对儿科消化疾病转化研究的大力关注。核心教员是生物医学信息学部的成员，生物医学信息学部是最先进的计算基础设施的所在地，也是辛辛那提儿童研究基金会 (CCRF) 生物信息学研究和培训的中心。 该核心为研究的数据处理、分析和结果解释提供支持，这些技术使用的技术包括基因表达微阵列、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、蛋白质-蛋白质和蛋白质-药物相互作用的蛋白质结构预测。为此，生物信息学核心使用一系列资源，这些资源由生物医学信息学部门内的基础设施专家进行物理管理。 DHC 调查人员可以直接访问核心服务，并且获得针对其项目需求的个性化支持，以便不仅从自己的遗传和基因组数据中获得知识，而且还可以利用多个其他内部和外部研究数据来优化知识获取。通过在概念阶段提供核心咨询服务，调查结果也得到了改善；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；并通过综合数据挖掘、结果解读；讨论适当的验证、实验外推和出版。该核心服务于 DHC 所有四个重点领域的项目研究需求：1) 慢性肝病，2) 炎症和腹泻病，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）和非酒精性脂肪肝的分子基础和机制产生了新的见解——所有这些都是发病机制复杂的疾病，也是儿童大量发病和死亡的原因—— 还为探索胃肠道干细胞和祖细胞体内和体外形成和功能的基本发育生物学和转化影响的研究做出了重要贡献。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，这些培训受到了热烈的关注并带来了积极的参与和合作。 核心领导层在加强 DHC 研究人员研究的目标上具有创新性。满足 DHC 项目的需求一直是独立资助项目背后的驱动力，这些项目开发了新颖的计算工具来分析和推断导致疾病的关键基因和机制，例如 GATACA、Toppgene 和 Toppcluster，这是一套用于聚合、挖掘和可视化基因、途径和疾病表型知识的综合工具套件。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 调查人员的数据与广泛的其他可用数据（例如来自 NCBI GEO 的数据）相结合，开发了消化组数据库，其目的是使 DHC 调查人员能够进行数据分析和挖掘，以形成对消化系统发育和疾病的新假设和理解。在 CCRF 的大力支持下，Core 与基因和蛋白质表达核心合作，现已实施了丰富的集成工具来分析下一代测序衍生数据，包括外显子组测序、RNA-seq 和 ChIP-seq，并且 DHC 研究人员已在 EE、IBD 和干细胞相关项目中使用这些工具。因此，本摘要强调了动态的生物信息学核心，该核心为 DHC 研究人员提供最先进的服务，充当协作和创新的核心，并不断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。