Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis

• DOI: 10.1093/braincomms/fcaa053
• Publication Date: 2020-06-17T12:25:24Z
• Authors: Greig Joilin; Elizabeth Gray; Alexander G Thompson; Yoana Bobeva; Kevin Talbot; Jochen Weishaupt; Albert Ludolph; Andrea Malaspina; P Nigel Leigh; Sarah F Newbury; Martin R Turner; Majid Hafezparast
• Keywords: 0301 basic medicine; 03 medical and health sciences; Q0179.9; Original Article; Q1

Abstract Objective biomarkers for the clinically heterogeneous adult-onset neurodegenerative disorder amyotrophic lateral sclerosis are crucial to facilitate assessing emerging therapeutics and improve diagnostic pathway in what is a syndrome. With non-coding RNA transcripts including microRNA, piwi-RNA transfer present human biofluids, we sought identify whether serum could be sclerosis. Serum samples from our Oxford Study Biomarkers motor neurone disease/amyotrophic discovery cohort of patients (n = 48), disease mimics 16) age- sex-matched healthy controls 24) were profiled expression using RNA-sequencing, which showed wide range dysregulated. We confirmed significant alterations with reverse transcription-quantitative PCR hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-92a-3p, hsa-piR-33151, TRV-AAC4-1.1 TRA-AGC6-1.1. Furthermore, hsa-miR-206, previously identified biomarker, binary-like pattern samples. Using these RNA, able discriminate random forest analysis 93.7% accuracy promise predicting progression rate patients. Importantly, cross-validation this novel signature new geographically distinct United Kingdom Germany both control 156) yielded an 73.9%. The high prediction RNA-based biomarker signature, even across cohorts, demonstrates strength approach as platform stratify