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

Autor: Julie J. Paik, José C. Milisenda, Lisa Christopher-Stine, Andrea M. Corse, Frederick W. Miller, Andrew L. Mammen, Carme Carrion-Ribas, Josep Maria Grau-Junyent, Jemima Albayda, Assia Derfoul, Thomas E. Lloyd, Katherine Pak, Albert Selva-O'Callaghan, Iago Pinal-Fernandez, Maria Casal-Dominguez
Rok vydání: 2019
Předmět:
Male
Biopsy
Cell Culture Techniques
Antisynthetase syndrome
computer.software_genre
Polymyositis
Machine Learning
Mice
0302 clinical medicine
Mucoproteins
Immunology and Allergy
Myositis
biology
Early Growth Response Transcription Factors
Female
medicine.symptom
Algorithm
Adult
Immunology
Machine learning
General Biochemistry
Genetics and Molecular Biology
Dermatomyositis
Autoimmune Diseases
Myositis
Inclusion Body
03 medical and health sciences
Rheumatology
Muscular Diseases
medicine
Addressin
Animals
Humans
Myopathy
Muscle
Skeletal
Apolipoproteins A
030203 arthritis & rheumatology
business.industry
Interleukin-8
Autoantibody
medicine.disease
Calcium-Calmodulin-Dependent Protein Kinase Type 1
biology.protein
Hydroxymethylglutaryl CoA Reductases
Artificial intelligence
Inclusion body myositis
business
Transcriptome
computer
Cell Adhesion Molecules
030217 neurology & neurosurgery
Zdroj: Annals of the rheumatic diseases. 79(9)
ISSN: 1468-2060
Popis: ObjectivesMyositis 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.MethodsRNA-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.ResultsThe 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.ConclusionsUnique 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.
Databáze: OpenAIRE
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