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A Multimodal and Integrated Approach to Interrogate Human Kidney Biopsies with Rigor and Reproducibility: Guidelines from the Kidney Precision Medicine Project
Physiological Genomics ( IF 2.5 ) Pub Date : 2020-11-16 , DOI: 10.1152/physiolgenomics.00104.2020
Tarek M El-Achkar 1 , Michael T Eadon 1 , Rajasree Menon 2 , Blue B Lake 3 , Tara K Sigdel 4 , Theodore Alexandrov 5 , Samir Parikh 6 , Guanshi Zhang 7 , Dejan Dobi 4 , Kenneth W Dunn 1 , Edgar A Otto 2 , Christopher R Anderton 7, 8 , Jonas M Carson 9 , Jinghui Luo 2 , Chris Park 9 , Habib Hamidi 2 , Jian Zhou 10, 11 , Paul Hoover 12 , Andrew Schroeder 4 , Marianinha Joanes 4 , Evren U Azeloglu 13 , Rachel Sealfon 10, 11 , Seth Winfree 1 , Becky Steck 2 , Yongqun He 2 , Vivette D'Agati 11 , Ravi Iyengar 13 , Olga G Troyanskaya 10, 11 , Laura Barisoni 14 , Joseph Gaut 15 , Kun Zhang 3 , Zoltan Laszik 4 , Brad H Rovin 6 , Pierre C Dagher 1 , Kumar Sharma 7 , Minnie M Sarwal 4 , Jeffrey B Hodgin 2 , Charles E Alpers 9 , Matthias Kretzler 2 , Sanjay Jain 15
Affiliation  

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 3-dimensional (3D) molecular atlases of healthy and diseased kidney biopsies 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 3D 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 3D 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 being approved to interrogate clinical biopsy specimens. The process established economizes the use of valuable biopsy tissue for multi-OMICS 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.

中文翻译:

一种以严格性和可重复性审问人类肾脏活检的多模式和综合方法:来自肾脏精密医学项目的指南

在细胞水平上全面和空间映射的器官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) 致力于使用跨多个机构的多种最先进的 OMICS 和成像技术生成健康和患病肾脏活检的 3 维 (3D) 分子图谱。从不同的方法和在不同的位置获得严格和可重复的结果以在单细胞水平或 3D 空间中询问生物分子是一项重大挑战,如果控制不当可能是徒劳的。我们描述了一种“跟随组织”管道,用于生成可靠且真实的成人肾脏单细胞/区域 3D 分子图谱。我们的方法强调从样本采购、处理、存储、运输到数据生成、分析和共享的不同 OMICS 和成像技术之间的质量保证、质量控制、验证和协调。我们通过使用在不同机构和不同技术中处理和分析的共同来源组织进行的试点实验,为跨多种技术的质量控制、严谨性、可重复性和可行性建立了基准。在被批准用于询问临床活检标本之前,建立了同行评审系统,以严格审查质量控制措施和每种技术生成的数据的可重复性。
更新日期:2020-11-17
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