Open AccessA multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: guidelines from the Kidney Precision Medicine Project
Author(s) -
Tarek M. ElAchkar,
Michael T. Eadon,
Rajasree Me,
Blue B. Lake,
Tara K. Sigdel,
Theodore Alexandrov,
Samir Parikh,
Guanshi Zhang,
Deján Dobi,
Kenneth W. Dunn,
Edgar A. Otto,
Christopher Anderton,
Jonas 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. D’Agati,
Ravi Iyengar,
Olga G. Troyanskaya,
Laura Barisoni,
Joseph P. Gaut,
Kun Zhang,
Zoltán Lászik,
Brad H. Rovin,
Pierre C. Dagher,
Kumar Sharma,
Minnie M. Sarwal,
Jeffrey B. Hodgin,
Charles E. Alpers,
Matthias Kretzler,
Sanjay Jain
Publication year - 2021
Publication title -
physiological genomics/physiological genomics (print)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.078
H-Index - 112
eISSN - 1531-2267
pISSN - 1094-8341
DOI - 10.1152/physiolgenomics.00104.2020
Subject(s) - precision medicine , quality assurance , computer science , medical physics , personalized medicine , data science , quality (philosophy) , biology , bioinformatics , medicine , pathology , external quality assessment , philosophy , epistemology
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.