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Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry

Fan Zhang, Kevin Wei, Kamil Slowikowski, Chamith Y. Fonseka, Deepak A. Rao, Stephen Kelly, Susan M. Goodman, Darren Tabechian, Laura B. Hughes, Karen Salomon-Escoto, Gerald F. M. Watts, William Apruzzese, David J. Lieb, David L. Boyle, Arthur M. Mandelin II, Accelerating Medicines Partnership: RA Phase 1, AMP RA/SLE, Brendan F. Boyce, Edward DiCarlo, Ellen M. Gravallese, Peter K. Gregersen, Larry Moreland, Gary S. Firestein, Nir Hacohen, Chad Nusbaum, James A. Lederer, Harris Perlman, Costantino Pitzalis, Andrew Filer, V. Michael Holers, Vivian P. Bykerk, Laura T. Donlin, Jennifer H. Anolik, Michael B. Brenner, Soumya Raychaudhuri
doi: https://doi.org/10.1101/351130
Fan Zhang
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Division of Rheumatology and Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115 USA
4Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, MA 02142, USA
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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Kevin Wei
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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Kamil Slowikowski
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Division of Rheumatology and Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115 USA
4Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, MA 02142, USA
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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Chamith Y. Fonseka
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Division of Rheumatology and Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115 USA
4Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, MA 02142, USA
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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Deepak A. Rao
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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Stephen Kelly
6Department of Rheumatology, Barts Health NHS Trust, London, E1 1BB, UK
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Susan M. Goodman
7Division of Rheumatology, Hospital for Special Surgery, New York, NY 10021, USA
8Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
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Darren Tabechian
9Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
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Laura B. Hughes
10Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA
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Karen Salomon-Escoto
11Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
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Gerald F. M. Watts
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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William Apruzzese
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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David J. Lieb
4Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, MA 02142, USA
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David L. Boyle
12Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA 92093 USA
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Arthur M. Mandelin II
13Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine. Chicago, IL 60611, USA
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14AMP RA Phase 1: full list of members and affiliations appears in the end of the paper
Brendan F. Boyce
15Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
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Edward DiCarlo
8Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
16Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY 10021, USA
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Ellen M. Gravallese
11Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
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Peter K. Gregersen
17Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY 11030, USA
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Larry Moreland
18Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA
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Gary S. Firestein
12Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA 92093 USA
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Nir Hacohen
4Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, MA 02142, USA
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Chad Nusbaum
4Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, MA 02142, USA
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James A. Lederer
19Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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Harris Perlman
13Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine. Chicago, IL 60611, USA
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Costantino Pitzalis
20Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, E1 4NS, UK
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Andrew Filer
21Rheumatology Research Group, Institute of Inflammation and Ageing, The University of Birmingham, Birmingham, B15 2WB, UK
22University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK
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V. Michael Holers
23Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO 80220, USA
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Vivian P. Bykerk
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA 02115, USA
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Laura T. Donlin
8Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
24Arthritis and Tissue Degeneration, Hospital for Special Surgery, New York, NY 10021, USA
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Jennifer H. Anolik
9Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
25Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
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Michael B. Brenner
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
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Soumya Raychaudhuri
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA 02115, USA
2Division of Rheumatology and Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115 USA
4Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, MA 02142, USA
5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
26Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK
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Article Information

doi 
https://doi.org/10.1101/351130
History 
  • June 20, 2018.
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Author Information

  1. Fan Zhang1,2,3,4,5,^,
  2. Kevin Wei5,^,
  3. Kamil Slowikowski1,2,3,4,5,^,
  4. Chamith Y. Fonseka1,2,3,4,5,^,
  5. Deepak A. Rao5,^,
  6. Stephen Kelly6,
  7. Susan M. Goodman7,8,
  8. Darren Tabechian9,
  9. Laura B. Hughes10,
  10. Karen Salomon-Escoto11,
  11. Gerald F. M. Watts5,
  12. William Apruzzese5,
  13. David J. Lieb4,
  14. David L. Boyle12,
  15. Arthur M. Mandelin II13,
  16. Accelerating Medicines Partnership: RA Phase 1, AMP RA/SLE14,
  17. Brendan F. Boyce15,
  18. Edward DiCarlo8,16,
  19. Ellen M. Gravallese11,
  20. Peter K. Gregersen17,
  21. Larry Moreland18,
  22. Gary S. Firestein12,
  23. Nir Hacohen4,
  24. Chad Nusbaum4,
  25. James A. Lederer19,
  26. Harris Perlman13,
  27. Costantino Pitzalis20,
  28. Andrew Filer21,22,
  29. V. Michael Holers23,
  30. Vivian P. Bykerk1,
  31. Laura T. Donlin8,24,*,
  32. Jennifer H. Anolik9,25,*,
  33. Michael B. Brenner5,* and
  34. Soumya Raychaudhuri1,2,3,4,5,26,*
    1. 1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA 02115, USA
    2. 2Division of Rheumatology and Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
    3. 3Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115 USA
    4. 4Broad Institute of Massachusetts Institute and Technology and Harvard University, Cambridge, MA 02142, USA
    5. 5Division of Rheumatology, Immunology, Allergy, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
    6. 6Department of Rheumatology, Barts Health NHS Trust, London, E1 1BB, UK
    7. 7Division of Rheumatology, Hospital for Special Surgery, New York, NY 10021, USA
    8. 8Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
    9. 9Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
    10. 10Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA
    11. 11Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    12. 12Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA 92093 USA
    13. 13Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine. Chicago, IL 60611, USA
    14. 14AMP RA Phase 1: full list of members and affiliations appears in the end of the paper
    15. 15Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
    16. 16Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY 10021, USA
    17. 17Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY 11030, USA
    18. 18Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 USA
    19. 19Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, MA 02115, USA
    20. 20Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, E1 4NS, UK
    21. 21Rheumatology Research Group, Institute of Inflammation and Ageing, The University of Birmingham, Birmingham, B15 2WB, UK
    22. 22University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK
    23. 23Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO 80220, USA
    24. 24Arthritis and Tissue Degeneration, Hospital for Special Surgery, New York, NY 10021, USA
    25. 25Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    26. 26Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK
    27. 27Translational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA
    28. 28Department of Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    29. 29Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA
    30. 30David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY 10021, USA
    31. 31Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
    32. 32The Rockefeller University, New York, NY 10065, USA
    33. 33Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94305, USA
    34. 34The Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, CA 94305, USA
    1. Correspondence and requests for materials should be addressed to, Soumya Raychaudhuri, 77 Avenue Louis Pasteur, Harvard New Research Building, Suite 250D, Boston, MA 02446, USA. soumya{at}broadinstitute.org; 617-525-4484 (tel); 617-525-4488 (fax)
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    Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry
    Fan Zhang, Kevin Wei, Kamil Slowikowski, Chamith Y. Fonseka, Deepak A. Rao, Stephen Kelly, Susan M. Goodman, Darren Tabechian, Laura B. Hughes, Karen Salomon-Escoto, Gerald F. M. Watts, William Apruzzese, David J. Lieb, David L. Boyle, Arthur M. Mandelin II, Accelerating Medicines Partnership: RA Phase 1, AMP RA/SLE, Brendan F. Boyce, Edward DiCarlo, Ellen M. Gravallese, Peter K. Gregersen, Larry Moreland, Gary S. Firestein, Nir Hacohen, Chad Nusbaum, James A. Lederer, Harris Perlman, Costantino Pitzalis, Andrew Filer, V. Michael Holers, Vivian P. Bykerk, Laura T. Donlin, Jennifer H. Anolik, Michael B. Brenner, Soumya Raychaudhuri
    bioRxiv 351130; doi: https://doi.org/10.1101/351130
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    Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry
    Fan Zhang, Kevin Wei, Kamil Slowikowski, Chamith Y. Fonseka, Deepak A. Rao, Stephen Kelly, Susan M. Goodman, Darren Tabechian, Laura B. Hughes, Karen Salomon-Escoto, Gerald F. M. Watts, William Apruzzese, David J. Lieb, David L. Boyle, Arthur M. Mandelin II, Accelerating Medicines Partnership: RA Phase 1, AMP RA/SLE, Brendan F. Boyce, Edward DiCarlo, Ellen M. Gravallese, Peter K. Gregersen, Larry Moreland, Gary S. Firestein, Nir Hacohen, Chad Nusbaum, James A. Lederer, Harris Perlman, Costantino Pitzalis, Andrew Filer, V. Michael Holers, Vivian P. Bykerk, Laura T. Donlin, Jennifer H. Anolik, Michael B. Brenner, Soumya Raychaudhuri
    bioRxiv 351130; doi: https://doi.org/10.1101/351130

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