DNA sequencing and Bioinformatics

DNA测序和生物信息学

基本信息

批准号：
10000993
负责人：
Dietrich A Stephan
金额：
$ 10.45万
依托单位：
UNIVERSITY OF GHANA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-18 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10000993
关键词：
Address Africa African Alleles Architecture Award Basic Science Bioinformatics Biological Cells Chairperson Comparison arm DNA DNA sequencing Data Data Analyses Data Set Education Ensure Functional disorder Funding Funding Applicant Generations Genetic Genome Genome Scan Genomics Genotype Glean Haplotypes Journals Location Mediation Nature Neurosciences Organ Pathogenesis Pathway interactions Phenotype Policies Population Positioning Attribute Predisposition Price Privatization Process Publishing Research Personnel Resolution Risk SNP array Sampling Science Services Sickle Cell Anemia Structure Testing Time Tissues Training Translations United States National Institutes of Health Ursidae Family Variant Work biobank causal variant clinical research site commercialization data sharing design experience experimental study follow-up genome analysis genome wide association study genome-wide analysis human data innovation insight interest new technology novel novel diagnostics novel therapeutics phenotypic data screening success targeted treatment therapeutic development

项目摘要

Summary The Shared Bioinformatics Core that is proposed to support the Projects of SickleGenAfrica addresses a critical problem in the effort to generate new insights into pathogenesis of organ damage in sickle cell disease populations in Africa: namely access to a high throughput and high quality genome scanning and analysis center that is deeply experienced in GWAS. The leader of this Core has processed and analyzed tens of thousands of genotyping arrays, led large consortia in the form of the U54 mechanism (as Chairman of the NIH Neuroscience Microarray Consortium), and provided new insights into pathobiology that have been published in journals such as Cell, Nature Genetics, NEJM, and Science. The key critical barrier that the Core solves is access to deep experience with genome scanning and analysis. When the aims of this Shared Core are achieved, we will have generated a training set of data that will be used to identify novel correlations between small ancient haplotype blocks and several SCD-related phenotypes. More generally, this data will be used to refine locations of causative variants, and also form a component of a collaborative data set that informs genomic architecture from across the African continent. These new insights into predisposition alleles will enable a more refined understanding of the pathogenesis of organ dysfunction that the Projects are focused on, which can then be parlayed into risk screening or targeted therapeutic development. The successful completion of the aims of this Core will utilize new technology, the H3Africa array, which is the latest innovation in array design specific to African populations, derived from both public and private sequencing data sets. This new and most comprehensive view of the ancient African genomes derived from the work in this Core will allow us to get unprecedented resolution into the variants that are correlated to, and enhance risk for, some of the most prevalent complications of SCD, which may form the basis for new diagnostic and therapeutic development. Importantly, the Core leader has led the field in translation and commercialization of such new insights in the form of products/companies (such as Navigenics) that deliver solutions to the population, connecting the dots from taxpayer funded basic research, and is a differentiator of this Core.

概括旨在支持镰刀法项目的共享生物信息学核心解决了努力为镰状细胞病中器官损伤发病的新见解的关键问题非洲人口：即获得高吞吐量和高质量的基因组扫描和分析在GWAS中经验丰富的中心。该核心的领导者已经处理和分析了数十个成千上万的基因分型阵列，以U54机制的形式领导大财团（作为NIH主席神经科学微阵列联盟），并提供了有关病原体学的新见解在细胞，自然遗传学，NEJM和科学等期刊中。核心解决的关键关键障碍是获得基因组扫描和分析的深厚经验。当这个共享核心的目标是达到的，我们将生成一组培训数据，这些数据将用于识别新的相关性小型古代单倍型块和几种与SCD相关的表型。更一般地，这些数据将用于优化因果变体的位置，还构成了协作数据集的组成部分来自非洲大陆的基因组建筑。这些对倾向等位基因的新见解将使对器官功能障碍的发病机理具有更精致的理解，即项目集中然后，可以将其分解为风险筛查或有针对性的治疗发育。成功该核心目标的完成将利用新技术H3africa阵列，这是最新的创新在特定于非洲人群的阵列设计中，源自公共和私人测序数据集。这从该核心的工作中得出的古代非洲基因组的新的，最全面的看法将允许我们要将与与某些变体相关的变体中的前所未有的解决方案。 SCD的最普遍并发症，这可能是新诊断和治疗的基础发展。重要的是，核心领导者领导了这种新的翻译和商业化的领域以产品/公司（例如Navigenics）形式的见解，这些洞察力为人口提供解决方案，连接纳税人资助的基础研究的点，是该核心的区别。