A Multimodal and Integrated Approach to Interrogate Human Kidney Biopsies with Rigor and Reproducibility: The Kidney Precision Medicine Project

摘要: Abstract Comprehensive and spatially mapped molecular atlases of organs at a cellular level are critical resource to gain insights into pathogenic mechanisms therapies tailored the disease each patient. Obtaining rigorous reproducible results from disparate methods different sites interrogate biomolecules single cell or in 3-dimensional (3D) space is significant challenge that can be futile exercise if not well controlled. The Kidney Precision Medicine Project (KPMP) an endeavor generate 3D healthy diseased kidney biopsies using multiple state-of-the-art OMICS imaging technologies across several institutions. We describe pipeline for generating reliable authentic cell/region atlas human adult with emphasis on quality assurance, control, validation harmonization methods. Our “follow tissue” approach encompasses sample procurement data generation, analysis, sharing, while standardizing, harmonizing procedures collection, processing, storage shipping. provide key features preanalytical parameters, bioassays, post analyses, reference standards depositions. A pilot experiment common source tissue processed analyzed institutions was executed identify potential sources variation, feasibility multimodal analyses unique redundant macromolecules being characterized by technology. An important outcome identification limitations strengths technologies, how composite information leveraged clinical application. peer review system established critically control measures reproducibility generated technology before granting approval work biopsy specimens. This establishes process economizes use valuable multi-OMICS analysis stringent ensure rigor which serve as model similar personalized medicine projects. Author Contributions MTE, RM, BBL, TS, TA, AS, SP, CRA, DD, EAO, SW, GZ, MJ KD performed ground group, wrote KPMP TIS manual figures. HH, JZ, RS, TME, PH, MK, ZL SJ initial working marker list. CEA, JBH, JL, MK led Pilot 1 protocol. VD, LB, JG, ZL, JBH developed pathology QC qualification processing criteria. organized collection distribution. JC designed SpecTrack system. CP prepared organization services. YH ontology development metadata knowledge standardization. BS EA integration efforts authentication hub. KS MS discussion group. TME CEA MTE Molecular Pathology Integration conceived TISAC process. RI, OGT KZ, BR, PCD, KS, MS, integrated vision. draft paper. All authors contributed writing editing manuscript.