GTEx engagement with the CFDE-CC and other DCCs towards building a data ecosystem spanning the Common Fund projects

GTEx 与 CFDE-CC 和其他 DCC 合作，构建涵盖共同基金项目的数据生态系统

• 批准号: 10683507
• 负责人: KRISTIN ARDLIE
• 金额: $ 95.62万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-23 至 2023-09-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10683507
• 关键词: Funding; Genotype-Tissue Expression Project; Text; data ecosystem

Detailed Engagement Plan The National Institutes of Health Common Fund’s Genotype-Tissue Expression (GTEx) project was launched in 2010 with a goal of providing the scientific community with a resource for the study of human gene expression and regulation across multiple tissues, to specifically provide insights into the mechanisms of gene regulation and disease-related perturbations, and to further our understanding of the role that inherited genetic variation plays in susceptibility to complex diseases. The project enrolled 960 recently deceased, adult donors and collected close to 49,000 tissue samples. Core data generation was completed at the end of 2017, with the primary data types including whole genome (WGS, 30X) and whole exome (WES, 100X) sequence data on all donors, and RNA-sequence data from at least 25,000 samples spanning 53 human tissues/organs. This dataset constitutes the largest multi-tissue RNA sequence data resource generated to date (a previous study of genetic effects on gene expression, TwinsUK/EUROBATS, generated ~2,700 RNA-seq samples from four accessible tissue sites). The GTEx resource also includes a rich and well annotated collection of donor, sample, and experiment metadata. Furthermore, additional molecular data types, aimed at enhancing the core data sets, are still being produced, including mass spectrometry-based proteomics, measurements of DNA methylation, histone marks (ChIP-seq), somatic DNA sequencing, and DNase I hypersensitivity sites. The GTEx resource includes both protected-access and open-access data (Fig. 1). The protected-access data include extensive sample, subject and technical metadata and raw sequence BAM files from RNAseq, whole genome (WGS) and whole exome (WES) sequencing, ChIP-seq and m6A RNA-seq, as well as protected data derived from these such as genotype calls in VCF format. An approved dbGaP application is required to obtain all protected-access data, including access to the raw sequence data, which are accessible on the AnVIL platform (on Google Cloud Platform; GCP). The GTEx data also include a large amount of open-access data, such as gene and transcript expression quantifications, cis- and trans-expression and splicing QTLs, histology images of every tissue, some eGTEx data summaries, the sample biobank, and a very limited set of de-identified sample and subject metadata. All of these public data are available for download, and as interactive visualizations and summary tables on the GTEx portal. The GTEx project has developed an extensive suite of tools and analysis pipelines that have been benchmarked, optimized and implemented in GCP for the project (such as the RNA-seq alignment, quantification, and QC pipeline, and the QTL analysis pipeline). These pipelines were also selected by the TOPMed project to produce a harmonized resource of RNA sequence data across the large number of cohorts being sequenced for that project (>20,000 samples to date); our team was involved in initial benchmarking and harmonization tests of our pipeline across TOPMed sequencing centers and are actively involved in ongoing data production and analyses. Moreover, very similar pipelines are used by the ENCODE project, thus facilitating comparisons across large datasets that would be prohibitive in terms of costs and computational resources in the absence of harmonized pipelines. We have also created numerous visualizations developed specifically for the open access data on the GTEx portal. The GTEx project has a very large user community: the GTEx data have the second largest number of Data Access Requests for protected data in dbGaP (behind TCGA), and it is the most frequently downloaded dbGaP project. An even larger number of users access the data, tools and interactive visualizations on the GTEx portal: in the 2019 calendar year, the GTEx portal had 135,000 users (~12,000-18,000/month) worldwide, with users spiking in October 2019 following the release of the V8 data. The GTEx consortium has published numerous papers describing the dataset and analyses of the data, and two additional data releases are still planned.

详细的参与计划 美国国立卫生研究院普通​​基金的基因型组织表达（GTEX）项目是 于2010年启动，目的是为科学界提供研究人类的资源 跨多个时机的基因表达和调节，以专门提供有关机制的见解 基因调节和与疾病相关的扰动，并进一步了解我们对 遗传性遗传变异对复杂疾病的敏感性发挥作用。该项目最近注册了960 已故的成年捐助者，收集了近49,000个组织样本。核心数据生成是 于2017年底完成，主要数据类型在内 所有供体的外显子（WES，100倍）序列数据，以及来自至少25,000个样本的RNA序列数据 跨越53种人体组织/器官。该数据集构成最大的多组织RNA序列数据 迄今为止生成的资源（先前研究了对基因表达的遗传影响，Twinsuk/Eurobats， 从四个可访问的组织部位产生了约2,700个RNA-seq样品）。 GTEX资源还包括 供体，样本和实验元数据的丰富且注释良好的集合。此外，附加 旨在增强核心数据集的分子数据类型仍在生产中，包括质量 基于光谱法的蛋白质组学，DNA甲基化的测量，组蛋白标记（CHIP-SEQ），体细胞 DNA测序和DNase I超敏反应。 GTEX资源既包含受保护的访问和开放访问数据（图1）。受保护的访问 数据包括大量样本，主题和技术元数据以及RNASEQ的原始序列BAM文件， 全基因组（WGS）和整个外显子组（WES）测序，芯片序列和M6A RNA-Seq以及 源自这些的受保护数据，例如以VCF格式调用的基因型调用。批准的DBGAP申请 需要获取所有受保护的访问数据，包括访问原始序列数据， 在砧台平台（在Google Cloud Platform上； GCP）上访问。 GTEX数据还包括一个大的 开放访问数据的量，例如基因和转录本表达量化，顺式和反表达 和剪接QTL，每个组织的组织学图像，某些EGTEX数据摘要，样品 生物库，以及一组非常有限的去识别样品和受试者元数据。所有这些公共数据是 可供下载，作为GTEX门户网站上的交互式可视化和摘要表。 GTEX项目已经开发了一系列广泛的工具和分析管道 在GCP中针对项目的基准测试，优化和实施（例如RNA-seq Alignment， 定量和QC管道以及QTL分析管道）。这些管道也由 顶级项目，可在大量的 该项目的同类人群被测序（迄今为止> 20,000个样本）；我们的团队参与了初始 跨顶级测序中心对管道的基准测试和协调测试，并积极地 参与正在进行的数据生产和分析。此外，使用的管道非常相似 编码项目，从而支持大型数据集的比较 在没有协调管道的情况下，成本和计算资源。我们也创建了 专门为GTEX门户上的开放访问数据而开发了许多可视化。 GTEX 项目具有非常大的用户社区：GTEX数据具有第二大数据访问 DBGAP（在TCGA后面）中要求受保护数据的请求，它是最常见的DBGAP 项目。更多的用户访问GTEX上的数据，工具和交互式可视化 门户网站：在2019日历年，GTEX门户网站在全球范围 随着用户在2019年10月发行V8数据后的峰值。 GTEX财团已出版 描述数据集和数据分析的许多论文，以及两个其他数据发布 仍然计划。