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Towards Building a Smart Kidney Atlas: Network-based integration of multimodal transcriptomic, proteomic, metabolomic and imaging data in the Kidney Precision Medicine Project

Jens Hansen, Rachel Sealfon, Rajasree Menon, Michael T. Eadon, Blue B. Lake, Becky Steck, Dejan Dobi, Samir Parikh, Tara K. Sidgel, Theodore Alexandrov, Andrew Schroeder, Edgar A. Otto, Christopher R. Anderton, Daria Barwinska, Guanshi Zheng, Michael P. Rose, John P. Shapiro, Dusan Velickovic, Annapurna Pamreddy, Seth Winfree, Yongqun He, Ian H. de Boer, Jeffrey B. Hodgin, Abhijit Nair, Kumar Sharma, Minnie Sarwal, Kun Zhang, Jonathan Himmelfarb, Zoltan Laszik, Brad Rovin, Pierre C. Dagher, John Cijiang He, Tarek M. El-Achkar, Sanjay Jain, Olga G. Troyanskaya, Matthias Kretzler, Ravi Iyengar, Evren U. Azeloglu, for the Kidney Precision Medicine Project Consortium
doi: https://doi.org/10.1101/2020.07.23.216507
Jens Hansen
1Icahn School of Medicine at Mount Sinai, New York, New York
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Rachel Sealfon
2Princeton University, Princeton, New Jersey and Flatiron Institute, New York, New York
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Rajasree Menon
3University of Michigan School of Medicine, Ann Arbor, Michigan
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Michael T. Eadon
4Indiana University School of Medicine, Indianapolis, Indiana
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Blue B. Lake
5University of California San Diego, Jacobs School of Engineering, San Diego, California
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Becky Steck
3University of Michigan School of Medicine, Ann Arbor, Michigan
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Dejan Dobi
6University of California San Francisco School of Medicine, San Francisco, California
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Samir Parikh
7Ohio State University College of Medicine, Columbus, Ohio
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Tara K. Sidgel
6University of California San Francisco School of Medicine, San Francisco, California
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Theodore Alexandrov
8European Molecular Biology Laboratory, Heidelberg, Germany
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Andrew Schroeder
6University of California San Francisco School of Medicine, San Francisco, California
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Edgar A. Otto
3University of Michigan School of Medicine, Ann Arbor, Michigan
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Christopher R. Anderton
9Pacific Northwest National Laboratory, Richland, Washington
10UT-Health San Antonio School of Medicine, San Antonio, Texas
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Daria Barwinska
4Indiana University School of Medicine, Indianapolis, Indiana
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Guanshi Zheng
10UT-Health San Antonio School of Medicine, San Antonio, Texas
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Michael P. Rose
3University of Michigan School of Medicine, Ann Arbor, Michigan
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John P. Shapiro
7Ohio State University College of Medicine, Columbus, Ohio
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Dusan Velickovic
9Pacific Northwest National Laboratory, Richland, Washington
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Annapurna Pamreddy
10UT-Health San Antonio School of Medicine, San Antonio, Texas
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Seth Winfree
4Indiana University School of Medicine, Indianapolis, Indiana
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Yongqun He
3University of Michigan School of Medicine, Ann Arbor, Michigan
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Ian H. de Boer
11University of Washington, Schools of Medicine and Public Health, Seattle, Washington
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Jeffrey B. Hodgin
3University of Michigan School of Medicine, Ann Arbor, Michigan
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Abhijit Nair
3University of Michigan School of Medicine, Ann Arbor, Michigan
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Kumar Sharma
10UT-Health San Antonio School of Medicine, San Antonio, Texas
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Minnie Sarwal
6University of California San Francisco School of Medicine, San Francisco, California
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Kun Zhang
5University of California San Diego, Jacobs School of Engineering, San Diego, California
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Jonathan Himmelfarb
11University of Washington, Schools of Medicine and Public Health, Seattle, Washington
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Zoltan Laszik
6University of California San Francisco School of Medicine, San Francisco, California
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Brad Rovin
7Ohio State University College of Medicine, Columbus, Ohio
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Pierre C. Dagher
4Indiana University School of Medicine, Indianapolis, Indiana
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John Cijiang He
1Icahn School of Medicine at Mount Sinai, New York, New York
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Tarek M. El-Achkar
4Indiana University School of Medicine, Indianapolis, Indiana
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Sanjay Jain
12Washington University in Saint Louis School of Medicine, St. Louis, Missouri
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Olga G. Troyanskaya
2Princeton University, Princeton, New Jersey and Flatiron Institute, New York, New York
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  • For correspondence: evren.azeloglu@mssm.edu ravi.iyengar@mssm.edu kretzler@med.umich.edu ogt@genomics.princeton.edu
Matthias Kretzler
3University of Michigan School of Medicine, Ann Arbor, Michigan
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  • For correspondence: evren.azeloglu@mssm.edu ravi.iyengar@mssm.edu kretzler@med.umich.edu ogt@genomics.princeton.edu
Ravi Iyengar
1Icahn School of Medicine at Mount Sinai, New York, New York
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  • For correspondence: evren.azeloglu@mssm.edu ravi.iyengar@mssm.edu kretzler@med.umich.edu ogt@genomics.princeton.edu
Evren U. Azeloglu
1Icahn School of Medicine at Mount Sinai, New York, New York
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  • For correspondence: evren.azeloglu@mssm.edu ravi.iyengar@mssm.edu kretzler@med.umich.edu ogt@genomics.princeton.edu
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Abstract

The Kidney Precision Medicine Project (KPMP) plans to construct a spatially specified tissue atlas of the human kidney at a cellular resolution with near comprehensive molecular details. The atlas will have maps of healthy, acute kidney injury and chronic kidney disease tissues. To construct such maps, we integrate different data sets that profile mRNAs, proteins and metabolites collected by five KPMP Tissue Interrogation Sites. Here, we describe a set of hierarchical analytical methods to process, combine, and harmonize single-cell, single-nucleus and subsegmental laser microdissection (LMD) transcriptomics with LMD and near single-cell proteomics, 3-D nondestructive and immunofluorescence-based Codex imaging and spatial metabolomics datasets. We use nephrectomy, healthy living donor and surveillance transplant biopsy tissues to create a harmonized reference tissue map. Our results demonstrate that different assays produce reliable and coherent identification of cell types and tissue subsegments. They further show that the molecular profiles and pathways are partially overlapping yet complementary for cell type-specific and subsegmental physiological processes. Focusing on the proximal tubules, we find that our integrated systems biologybased analyses identify different subtypes of tubular cells with potential for different levels of lipid oxidation and energy generation. Integration of our omics data with pathways from the literature, enables us to construct predictive computational models to develop a smart kidney atlas. These integrated models can describe physiological capabilities of the tissues based on the underlying cell types and pathways in health and disease.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://kpmp.org

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Towards Building a Smart Kidney Atlas: Network-based integration of multimodal transcriptomic, proteomic, metabolomic and imaging data in the Kidney Precision Medicine Project
Jens Hansen, Rachel Sealfon, Rajasree Menon, Michael T. Eadon, Blue B. Lake, Becky Steck, Dejan Dobi, Samir Parikh, Tara K. Sidgel, Theodore Alexandrov, Andrew Schroeder, Edgar A. Otto, Christopher R. Anderton, Daria Barwinska, Guanshi Zheng, Michael P. Rose, John P. Shapiro, Dusan Velickovic, Annapurna Pamreddy, Seth Winfree, Yongqun He, Ian H. de Boer, Jeffrey B. Hodgin, Abhijit Nair, Kumar Sharma, Minnie Sarwal, Kun Zhang, Jonathan Himmelfarb, Zoltan Laszik, Brad Rovin, Pierre C. Dagher, John Cijiang He, Tarek M. El-Achkar, Sanjay Jain, Olga G. Troyanskaya, Matthias Kretzler, Ravi Iyengar, Evren U. Azeloglu, for the Kidney Precision Medicine Project Consortium
bioRxiv 2020.07.23.216507; doi: https://doi.org/10.1101/2020.07.23.216507
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Towards Building a Smart Kidney Atlas: Network-based integration of multimodal transcriptomic, proteomic, metabolomic and imaging data in the Kidney Precision Medicine Project
Jens Hansen, Rachel Sealfon, Rajasree Menon, Michael T. Eadon, Blue B. Lake, Becky Steck, Dejan Dobi, Samir Parikh, Tara K. Sidgel, Theodore Alexandrov, Andrew Schroeder, Edgar A. Otto, Christopher R. Anderton, Daria Barwinska, Guanshi Zheng, Michael P. Rose, John P. Shapiro, Dusan Velickovic, Annapurna Pamreddy, Seth Winfree, Yongqun He, Ian H. de Boer, Jeffrey B. Hodgin, Abhijit Nair, Kumar Sharma, Minnie Sarwal, Kun Zhang, Jonathan Himmelfarb, Zoltan Laszik, Brad Rovin, Pierre C. Dagher, John Cijiang He, Tarek M. El-Achkar, Sanjay Jain, Olga G. Troyanskaya, Matthias Kretzler, Ravi Iyengar, Evren U. Azeloglu, for the Kidney Precision Medicine Project Consortium
bioRxiv 2020.07.23.216507; doi: https://doi.org/10.1101/2020.07.23.216507

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