Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis

Iago Pinal-Fernandez, Maria Casal-Dominguez, Assia Derfoul, Katherine Pak, Frederick W. Miller, Jose César Milisenda, Josep Maria Grau-Junyent, Albert Selva-O'callaghan, Carme Carrion-Ribas, Julie J. Paik, Jemima Albayda, Lisa Christopher-Stine, Thomas E. Lloyd, Andrea M. Corse, Andrew L. Mammen

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives Myositis is a heterogeneous family of diseases that includes dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM), inclusion body myositis (IBM), polymyositis and overlap myositis. Additional subtypes of myositis can be defined by the presence of myositis-specific autoantibodies (MSAs). The purpose of this study was to define unique gene expression profiles in muscle biopsies from patients with MSA-positive DM, AS and IMNM as well as IBM. Methods RNA-seq was performed on muscle biopsies from 119 myositis patients with IBM or defined MSAs and 20 controls. Machine learning algorithms were trained on transcriptomic data and recursive feature elimination was used to determine which genes were most useful for classifying muscle biopsies into each type and MSA-defined subtype of myositis. Results The support vector machine learning algorithm classified the muscle biopsies with >90% accuracy. Recursive feature elimination identified genes that are most useful to the machine learning algorithm and that are only overexpressed in one type of myositis. For example, CAMK1G (calcium/calmodulin-dependent protein kinase IG), EGR4 (early growth response protein 4) and CXCL8 (interleukin 8) are highly expressed in AS but not in DM or other types of myositis. Using the same computational approach, we also identified genes that are uniquely overexpressed in different MSA-defined subtypes. These included apolipoprotein A4 (APOA4), which is only expressed in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) myopathy, and MADCAM1 (mucosal vascular addressin cell adhesion molecule 1), which is only expressed in anti-Mi2-positive DM. Conclusions Unique gene expression profiles in muscle biopsies from patients with MSA-defined subtypes of myositis and IBM suggest that different pathological mechanisms underly muscle damage in each of these diseases.

Original languageEnglish (US)
Pages (from-to)1234-1242
Number of pages9
JournalAnnals of the rheumatic diseases
Volume79
Issue number9
DOIs
StatePublished - Sep 1 2020

Keywords

  • autoantibodies
  • autoimmune diseases
  • autoimmunity
  • dermatomyositis
  • polymyositis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis'. Together they form a unique fingerprint.

Cite this