Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Fan Zhang, Anna Helena Jonsson, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Gerald FM Watts, Dana Weisenfeld, Kathryne E. Marks, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kathryn Weinand, Ellen M. Gravallese, Adam Chicoine, Kazuyoshi Ishigaki, Gregory Keras, Ilya Korsunsky, Zhihan J. Li, Yuhong Li, Yakir Reshef, Saori Sakaue, Zhu Zhu, Katherine P. Liao, Kevin Wei, Deepak A. Rao, Michael B. Brenner and Soumya Raychaudhuri
Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
Fan Zhang, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kathryn Weinand, Kazuyoshi Ishigaki, Ilya Korsunsky, Yakir Reshef, Saori Sakaue & Soumya Raychaudhuri
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Fan Zhang, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kathryn Weinand, Kazuyoshi Ishigaki, Ilya Korsunsky, Yakir Reshef, Saori Sakaue & Soumya Raychaudhuri
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
Fan Zhang, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kamil Slowikowski, Kathryn Weinand, Kazuyoshi Ishigaki, Ilya Korsunsky, Yakir Reshef, Saori Sakaue, Katherine P. Liao & Soumya Raychaudhuri
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Fan Zhang, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kamil Slowikowski, Kathryn Weinand, Kazuyoshi Ishigaki, Ilya Korsunsky, Yakir Reshef, Saori Sakaue & Soumya Raychaudhuri
Department of Rheumatology and the Center for Health Artificial Intelligence, University of Colorado School of Medicine, Aurora, CO, USA
Fan Zhang
Division of Immunology, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA
Maria Gutierrez-Arcelus
Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Bethesda, MD, USA
William Apruzzese
Rheumatology Research Group, Institute of Inflammation and Aging, University of Birmingham, Birmingham, UK
Saba Nayar, Mark Maybury, Ilfita Sahbudin, Hayley L. Carr, Karim Raza, Dagmar Scheel-Toellner & Andrew Filer
Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
Saba Nayar and Andrew Filer
Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Javier Rangel-Moreno, Nida Meednu, Darren Tabechian, Jennifer Albrecht, Jennifer L. Barnas, Debbie Campbell, Christopher Ritchlin & Jennifer H. Anolik
Hospital for Special Surgery, New York, NY, USA
Ian Mantel, Dana E. Orange, S. Louis Bridges Jr., Lionel B. Ivashkiv, Amit Lakhanpal, Anvita Singaraju, Melanie H. Smith, Susan M. Goodman, Vivian P. Bykerk & Laura T. Donlin
Weill Cornell Medicine, New York, NY, USA
Ian Mantel, S. Louis Bridges Jr., Lionel B. Ivashkiv, Amit Lakhanpal, Anvita Singaraju, Susan M. Goodman, Vivian P. Bykerk & Laura T. Donlin
Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.
Kamil Slowikowski
Laboratory of Molecular Neuro-Oncology, Rockefeller University, New York, NY, USA
Dana E. Orange
Department of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA
Laura Geraldino-Pardilla & Joan M. Bathon
Department of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
Kevin D. Deane, Jennifer A. Seifert, Larry W. Moreland, and V. Michael Holers
Department of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA.
Arnoldas Ceponis, Gary S. Firestein, and David L. Boyle
NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
Mark Maybury, Ilfita Sahbudin, Hayley L. Carr, Karim Raza, Dagmar Scheel-Toellner & Andrew Filer
Department of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Ami Ben-Artzi, Lindsy Forbess and Michael H. Weisman
Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Arthur M. Mandelin II & Harris Perlman
Center for Experimental Medicine and Rheumatology, EULAR Center of Excellence, William Harvey Research Institute, Queen Mary University of London, London, UK
Alessandra Nerviani, Myles J. Lewis, Felice Rivellese & Costantino Pitzalis
Barts Health NHS Trust, Barts Biomedical Research Center (BRC), National Institute for Health and Care Research (NIHR), London, UK
Alessandra Nerviani, Myles J. Lewis, Felice Rivellese & Costantino Pitzalis
Department of Biomedical Sciences, Humanitas University and Humanitas Research Hospital, Milan, Italy
Constantine Pitzalis
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Laura B. Hughes
Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA
Diane Horowitz and Peter K. Gregersen
Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY, USA
Edward DiCarlo
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
Brendan F Boyce
Department of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Mandy J. McGeachy & Larry W. Moreland
Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Andrew Cordle and Aaron Wyse
Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Patrick Dunn
Northrop Grumman Health Solutions, Rockville, MD, USA
Patrick Dunn
Division of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Joel M. Guthridge and Judith A. James
Laboratory of Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Kazuyoshi Ishigaki
Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
James A. Lederer
Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Andrew McDavid
Division of Immunology and Rheumatology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
William H. Robinson, Paul J. Utz, and Michael H. Weisman
LG-P., KDD, DT, AC, GSF, MM, IS, AB-A., AMM, A. Nerviani, FR, CP, LBH and DH recruited patients and obtained synovial tissues. LWM, SMG, HP, VMH, AF, VPB, and JHA contributed to sample acquisition and processing and design of the AMP study. ED, EMG and BFB performed histological assessment of tissues. DW, KPL, AF, and VPB compiled and analyzed histological and clinical data. WA provided project management and compiled histological and clinical data. K. Wei, AHJ, GFMW, A. Nathan, and MBB designed and implemented the tissue disaggregation, cell sorting, and single-cell sequencing pipeline. AHJ, K. Wei, and GFMW oversaw and executed the tissue disaggregation pipeline. S.N., J.R.-M. and N. Meednu. performed immunofluorescence microscopy and analyzed these data together with MC and AHJKEM and IM performed and analyzed functional cellular assays. MJL, FR, and CP contributed unpublished clinical trial data. FZ, A. Nathan, N. Millard, MC, QX, MG-A., JBK, K. Weinand, JM, LR, and SR performed computational and statistical analyses. AHJ, K. Wei, MBB, JHA, LTD, DAR, FZ, A. Nathan, SR, DEO, JR-M. and AF provided input on cellular analysis and interpretation. DEO, JR-M., AF and JHA provided input for histological analyses. N. Millard and KS implemented the website. SR, MBB, JHA, LTD, and DAR supervised the study. FZ, AHJ, A. Nathan, N. Millard, QX, and SR wrote the first draft. FZ, AHJ, A. Nathan, K. Wei, N. Millard, DAR, LTD, JHA, MBB, and SR edited the draft. Members of the AMP RA/SLE Network contributed to this work by managing patient recruitment, managing clinical data, obtaining and processing synovial tissue samples, managing biorepositories, performing histological or computational analyses, providing software code, providing website support and/or providing input for data analysis. and interpretation. All authors participated in editing the final manuscript.