Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integration of Synovial Histologic Features and RNA Sequencing Data

Arthritis & Rheumatology
Dana E OrangeLaura T Donlin

Abstract

In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning. Twenty histologic features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis [OA] patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes. Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C-reactive protein (CRP) levels were significantly...Continue Reading

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Citations

Jul 13, 2018·Arthritis Research & Therapy·Laura T DonlinJennifer H Anolik
Jan 9, 2019·The Korean Journal of Internal Medicine·Ki-Jo Kim, Ilias Tagkopoulos
Jan 23, 2020·Multiple Sclerosis : Clinical and Laboratory Research·Theresa L Wampler MuskardinTimothy B Niewold
Oct 16, 2019·Arthritis & Rheumatology·Dana E OrangeSusan M Goodman
Dec 1, 2019·Arthritis & Rheumatology·F RivelleseUNKNOWN PEAC-R4RA Investigators
Dec 1, 2019·Arthritis & Rheumatology·Dana E Orange, Laura T Donlin
Apr 30, 2019·Current Opinion in Rheumatology·Jessica A WalshYujin Park
Aug 29, 2020·Rheumatology International·Ankush D JamthikarJasjit S Suri
May 28, 2019·Frontiers in Medicine·Antonio ManzoSilvia Rossi
Jul 19, 2020·Clinical Reviews in Allergy & Immunology·Mengdi JiangPeter E Lipsky
Dec 10, 2019·Current Rheumatology Reports·Christopher Ritchlin, Jose U Scher
Dec 14, 2019·Scientific Reports·Konstantin CarlbergVivianne Malmström
Jul 28, 2020·Nature Reviews. Rheumatology·Daniel H Solomon, Robert S Rudin
Sep 8, 2018·Frontiers in Immunology·Deepak A Rao
Apr 20, 2019·Nature Reviews. Rheumatology·Laura T DonlinLionel B Ivashkiv
Apr 16, 2020·The American Journal of Surgical Pathology·Lingxin ZhangEdward F DiCarlo
May 21, 2020·Frontiers in Immunology·Alessandra NervianiCostantino Pitzalis
May 10, 2019·Science Translational Medicine·David KuoLaura T Donlin
Apr 6, 2019·Frontiers in Medicine·Clément Triaille, Bernard R Lauwerys
Oct 15, 2019·Arthritis Care & Research·Susan M GoodmanDana E Orange
Jun 30, 2019·Frontiers in Immunology·Askhat MyngbayJeannette Kunz
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Jan 22, 2021·Autoimmunity Reviews·Marie-Astrid BoutetFrédéric Blanchard
Mar 16, 2021·Frontiers in Genetics·Mateusz GarbulowskiJan Komorowski

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