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: 10468521
• 负责人: KRISTIN ARDLIE
• 金额: $ 41.41万
• 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/10468521
• 关键词: GTEx; engagement; CFDE; CC; other

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共同基金的基因型组织表达 (GTEx) 项目 于 2010 年推出，旨在为科学界提供研究人类的资源 跨多个组织的基因表达和调控，专门提供对机制的见解 基因调控和疾病相关的扰动，并进一步我们对作用的理解 遗传性基因变异影响复杂疾病的易感性 该项目最近招募了 960 名患者。 已故成年捐赠者并收集了近 49,000 个组织样本，生成了核心数据。 于2017年底完成，主要数据类型包括全基因组（WGS，30X）和全基因组 所有供体的外显子组（WES，100X）序列数据以及至少 25,000 个样本的 RNA 序列数据 该数据集涵盖 53 个人体组织/器官，构成了最大的多组织 RNA 序列数据。 迄今为止生成的资源（先前对基因表达的遗传影响的研究，TwinsUK/EUROBATS， 从四个可访问的组织位点生成了约 2,700 个 RNA-seq 样本）。 丰富且注释清晰的捐赠者、样本和实验元数据集合。 旨在增强核心数据集的分子数据类型仍在生产中，包括质量数据 基于光谱分析的蛋白质组学、DNA 甲基化测量、组蛋白标记 (ChIP-seq)、体细胞 DNA 测序和 DNase I 超敏位点。 GTEx 资源包括受保护访问和开放访问数据（图 1）。 数据包括来自 RNAseq 的大量样本、主题和技术元数据以及原始序列 BAM 文件， 全基因组 (WGS) 和全外显子组 (WES) 测序、ChIP-seq 和 m6A RNA-seq，以及 源自这些的受保护数据，例如 VCF 格式的基因型调用 经批准的 dbGaP 应用程序。 需要获取所有受保护的访问数据，包括对原始序列数据的访问，这些数据是 可在 AnVIL 平台（Google Cloud Platform；GCP）上访问 GTEx 数据还包括大量数据。 开放获取数据的数量，例如基因和转录本表达定量、顺式和反式表达 和剪接 QTL、每个组织的组织学图像、一些 eGTEx 数据摘要、样本 生物样本库，以及一组非常有限的去识别化样本和受试者元数据。 可供下载，并可在 GTEx 门户上以交互式可视化和汇总表的形式提供。 GTEx 项目开发了一套广泛的工具和分析流程， 在 GCP 中为该项目进行基准测试、优化和实施（例如 RNA-seq 比对、 定量、QC 管道和 QTL 分析管道）。 TOPMed 项目旨在生成跨大量 RNA 序列数据的统一资源 该项目正在对队列进行测序（迄今为止，我们的团队参与了最初的 20,000 个样本）； 我们正在积极对 TOPMed 测序中心的管道进行基准测试和协调测试 此外，它们使用非常相似的管道。 ENCODE 项目，从而促进大型数据集之间的比较，而这在 我们还创建了缺乏统一管道的成本和计算资源。 许多专门为 GTEx 门户上的开放访问数据开发的可视化。 项目拥有非常庞大的用户社区：GTEx数据拥有第二大数据访问量 对 dbGaP 中受保护数据的请求（仅次于 TCGA），并且是下载最频繁的 dbGaP 更多的用户在 GTEx 上访问数据、工具和交互式可视化。 门户：2019 年，GTEx 门户在全球拥有 135,000 名用户（约 12,000-18,000 名/月）， GTEx 联盟发布 V8 数据后，用户数量在 2019 年 10 月激增。 许多论文描述了数据集和数据分析，另外还有两个数据发布 仍在计划中。