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A Multimodal and Integrated Approach to Interrogate Human Kidney Biopsies with Rigor and Reproducibility: The Kidney Precision Medicine Project
bioRxiv - Scientific Communication and Education Pub Date : 2020-08-23 , DOI: 10.1101/828665
Tarek M. El-Achkar , Michael T. Eadon , Rajasree Menon , Blue B. Lake , Tara K. Sigdel , Theodore Alexandrov , Samir Parikh , Guanshi Zhang , Dejan Dobi , Kenneth W. Dunn , Edgar A. Otto , Christopher R. Anderton , Jonas M. Carson , Jinghui Luo , Chris Park , Habib Hamidi , Jian Zhou , Paul Hoover , Andrew Schroeder , Marianinha Joanes , Evren U. Azeloglu , Rachel Sealfon , Seth Winfree , Becky Steck , Yongqun He , Vivette D’Agati , Ravi Iyengar , Olga G Troyanskaya , Laura Barisoni , Joseph Gaut , Kun Zhang , Zoltan Laszik , Brad Rovin , Pierre C. Dagher , Kumar Sharma , Minnie Sarwal , Jeffrey B. Hodgin , Charles E. Alpers , Matthias Kretzler , Sanjay Jain ,

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:

多模式和集成的方法来询问人类肾脏活检的严谨性和可重复性:肾脏精密医学项目

在细胞水平上,器官的全面和空间定位的分子图谱是获取洞察疾病的致病机制和个性化疗法的重要资源。肾脏精密医学项目(KPMP)致力于在多个机构中使用多种最新的OMICS和成像技术来生成健康和患病肾脏活检的3维(3D)分子地图集。从不同的方法以及在不同的位置在单个细胞水平或3D空间中询问生物分子获得严格且可重复的结果是一项重大挑战,如果控制不好,这将是徒劳的。我们描述了一种遵循组织管道的技术,以生成人类成年肾脏的可靠且可靠的单细胞/区域3D分子图谱。我们的方法强调质量保证,从样品采购,处理,存储,运输到数据生成,分析和共享,跨不同的OMICS和成像技术进行质量控制,验证和协调。我们通过使用在不同机构和不同技术下进行处理和分析的共同来源组织进行的先导实验,建立了跨多种技术的质量控制,严格性,可再现性和可行性的基准。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产生的数据的可重复性,然后再批准对临床活检样本进行检查。
更新日期:2020-08-24
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