Machine Learning Analysis Using RNA Sequencing to Distinguish Neuromyelitis Optica from Multiple Sclerosis and Identify Therapeutic Candidates.

Autor:	Wylezinski LS; Decode Health, Inc., Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee., Sesler CL; Decode Health, Inc., Nashville, Tennessee., Shaginurova GI; Decode Health, Inc., Nashville, Tennessee., Grigorenko EV; Decode Health, Inc., Nashville, Tennessee., Wohlgemuth JG; Quest Diagnostics, Secaucus, New Jersey; Trusted Health Advisors, San Juan Capistrano, California., Cockerill FR 3rd; Decode Health, Inc., Nashville, Tennessee; Trusted Health Advisors, San Juan Capistrano, California; Department of Medicine, Rush University Medical Center, Chicago, Illinois., Racke MK; Quest Diagnostics, Secaucus, New Jersey., Spurlock CF 3rd; Decode Health, Inc., Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Wagner School of Public Service, New York University, New York, New York. Electronic address: chase@decodehealth.ai.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2024 Jun; Vol. 26 (6), pp. 520-529. Date of Electronic Publication: 2024 Mar 22.
DOI:	10.1016/j.jmoldx.2024.03.003
Abstrakt:	This study aims to identify RNA biomarkers distinguishing neuromyelitis optica (NMO) from relapsing-remitting multiple sclerosis (RRMS) and explore potential therapeutic applications leveraging machine learning (ML). An ensemble approach was developed using differential gene expression analysis and competitive ML methods, interrogating total RNA-sequencing data sets from peripheral whole blood of treatment-naïve patients with RRMS and NMO and healthy individuals. Pathway analysis of candidate biomarkers informed the biological context of disease, transcription factor activity, and small-molecule therapeutic potential. ML models differentiated between patients with NMO and RRMS, with the performance of certain models exceeding 90% accuracy. RNA biomarkers driving model performance were associated with ribosomal dysfunction and viral infection. Regulatory networks of kinases and transcription factors identified biological associations and identified potential therapeutic targets. Small-molecule candidates capable of reversing perturbed gene expression were uncovered. Mitoxantrone and vorinostat-two identified small molecules with previously reported use in patients with NMO and experimental autoimmune encephalomyelitis-reinforced discovered expression signatures and highlighted the potential to identify new therapeutic candidates. Putative RNA biomarkers were identified that accurately distinguish NMO from RRMS and healthy individuals. The application of multivariate approaches in analysis of RNA-sequencing data further enhances the discovery of unique RNA biomarkers, accelerating the development of new methods for disease detection, monitoring, and therapeutics. Integrating biological understanding further enhances detection of disease-specific signatures and possible therapeutic targets. (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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