A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: guidelines from the Kidney Precision Medicine Project
A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: guidelines from the Kidney Precision Medicine Project
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DOI：
10.1152/physiolgenomics.00104.2020
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发表时间：
2021-01-01
影响因子：
4.6
通讯作者：
Jain, Sanjay
中科院分区：
文献类型：
--
作者：
El-Achkar, Tarek M.;Eadon, Michael T.;Jain, Sanjay
在细胞水平上，器官的全面和空间映射的分子图谱是深入了解疾病的致病机制和个性化治疗的重要资源。肾脏精准医学项目（KPMP）是一项通过使用多个机构的最先进的组学和成像技术来生成健康和病变肾脏活检的三维（3-D）分子图谱的努力。从不同的方法和不同的地点获得严格的、可重复的结果，在单细胞水平或三维空间中询问生物分子是一项重大挑战，如果控制不好，可能是徒劳的。我们描述了一个“跟随组织”管道，用于生成可靠和真实的人类成人肾脏单细胞/区域3-D分子图谱。我们的方法强调从样品采购、处理、存储、运输到数据生成、分析和共享的不同组学和成像技术之间的质量保证、质量控制、验证和协调。通过使用在不同机构和不同技术下处理和分析的常见来源组织进行试点实验，我们建立了跨多种技术的质量控制、严谨性、可重复性和可行性的基准。建立了同行评议制度，在每种技术被批准用于询问临床活检标本之前，对质量控制措施和所产生数据的可重复性进行严格评议。所建立的过程节省了对有价值的活检组织进行多组学和成像分析的使用，并具有严格的质量控制，以确保结果的严谨性和可重复性，并可作为跨实验室，机构和财团的精准医学项目的模型。
Comprehensive and spatially mapped molecular atlases of organs at a cellular level are a critical resource to gain insights into pathogenic mechanisms and personalized therapies for diseases. The Kidney Precision Medicine Project (KPMP) is an endeavor to generate three-dimensional (3-D) molecular atlases of healthy and diseased kidney biopsies by using multiple state-of-the-art omics and imaging technologies across several institutions. Obtaining rigorous and reproducible results from disparate methods and at different sites to interrogate biomolecules at a single-cell level or in 3-D space is a significant challenge that can be a futile exercise if not well controlled. We describe a "follow the tissue" pipeline for generating a reliable and authentic single-cell/region 3-D molecular atlas of human adult kidney. Our approach emphasizes quality assurance, quality control, validation, and harmonization across different omics and imaging technologies from sample procurement, processing, storage, shipping to data generation, analysis, and sharing. We established benchmarks for quality control, rigor, reproducibility, and feasibility across multiple technologies through a pilot experiment using common source tissue that was processed and analyzed at different institutions and different technologies. A peer review system was established to critically review quality control measures and the reproducibility of data generated by each technology before their being approved to interrogate clinical biopsy specimens. The process established economizes the use of valuable biopsy tissue for multiomics and imaging analysis with stringent quality control to ensure rigor and reproducibility of results and serves as a model for precision medicine projects across laboratories, institutions and consortia.