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: 10444364
• 负责人: KRISTIN ARDLIE
• 金额: $ 15万
• 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/10444364
• 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）项目是 2010年启动，目标是为科学界提供研究人类疾病的资源。 跨多个组织的基因表达和调控，以具体提供对机制的见解， 基因调控和疾病相关的扰动，并进一步了解的作用， 遗传的基因变异在复杂疾病的易感性中起作用。该项目最近招收了960人 收集了近49，000份组织样本。核心数据生成是 于2017年底完成，主要数据类型包括全基因组（WGS，30 X）和全基因组 所有供体的外显子组（WES，100 X）序列数据，以及至少25，000份样本的RNA序列数据 跨越53个人体组织/器官。该数据集构成了最大的多组织RNA序列数据 迄今为止产生的资源（先前对基因表达的遗传效应的研究，TwinsUK/EUROBATS， 从四个可接近的组织位点产生约2，700个RNA-seq样品）。GTEx资源还包括 丰富且注释良好的供体、样本和实验元数据集合。此外，额外 旨在增强核心数据集的分子数据类型仍在制作中，包括质量数据 基于光谱的蛋白质组学，DNA甲基化测量，组蛋白标记（ChIP-seq），体细胞 DNA测序和DNA酶I超敏位点。 GTEx资源包括受保护访问和开放访问数据（图1）。受保护的访问 数据包括来自RNAseq的大量样品、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m6 A RNA-seq，以及 受保护的数据来源于这些，如VCF格式的基因型调用。已批准的dbGaP应用程序 需要获得所有受保护访问数据，包括访问原始序列数据， 可在AnVIL平台（Google Cloud Platform; GCP）上访问。GTEx数据还包括一个大型的 大量的开放获取数据，如基因和转录表达定量，顺式和反式表达 每个组织的组织学图像，一些eGTEx数据汇总，样品 生物库，以及一组非常有限的去识别样本和主题元数据。所有这些公开数据都是 可供下载，并作为交互式可视化和汇总表在GTEx门户网站。 GTEx项目开发了一套广泛的工具和分析管道， 在GCP中对项目进行基准测试、优化和实施（例如RNA-seq比对， 定量和QC流水线，以及QTL分析流水线）。这些管道也是由 TOPMed项目旨在为大量的RNA序列数据提供统一的资源， 该项目正在对队列进行测序（迄今为止超过20，000个样本）;我们的团队参与了最初的 在TOPMed测序中心对我们的管道进行基准测试和协调测试，并积极 参与持续的数据制作和分析。此外， ENCODE项目，从而促进了大型数据集之间的比较， 成本和计算资源，在缺乏统一的管道。也缔造 GTEx门户网站上专门为开放获取数据开发的众多可视化。GTEx 项目有一个非常大的用户社区：GTEx数据拥有第二大数据访问数量 请求dbGaP中受保护的数据（在TCGA之后），它是下载最频繁的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：在2019日历年，GTEx门户在全球拥有135，000名用户（约12，000 - 18，000/月）， 在V8数据发布后，用户在2019年10月达到峰值。GTEx联盟发布了 许多论文描述了数据集和数据分析，以及两个额外的数据发布， 仍在计划中。