Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis
Objective biomarkers for the clinically heterogeneous adult-onset neurodegenerative disorder amyotrophic lateral sclerosis are crucial to facilitate assessing emerging therapeutics and improve the diagnostic pathway in what is a clinically heterogeneous syndrome. With non-coding RNA transcripts incl...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2020
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| _version_ | 1826278306297675776 |
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| author | Joilin, G Gray, E Thompson, AG Bobeva, Y Talbot, K Weishaupt, J Ludolph, A Malaspina, A Leigh, PN Newbury, SF Turner, MR Hafezparast, M |
| author_facet | Joilin, G Gray, E Thompson, AG Bobeva, Y Talbot, K Weishaupt, J Ludolph, A Malaspina, A Leigh, PN Newbury, SF Turner, MR Hafezparast, M |
| author_sort | Joilin, G |
| collection | OXFORD |
| description | Objective biomarkers for the clinically heterogeneous adult-onset neurodegenerative disorder amyotrophic lateral sclerosis are crucial to facilitate assessing emerging therapeutics and improve the diagnostic pathway in what is a clinically heterogeneous syndrome. With non-coding RNA transcripts including microRNA, piwi-RNA and transfer RNA present in human biofluids, we sought to identify whether non-coding RNA in serum could be biomarkers for amyotrophic lateral sclerosis. Serum samples from our Oxford Study for Biomarkers in motor neurone disease/amyotrophic lateral sclerosis discovery cohort of amyotrophic lateral sclerosis patients (n = 48), disease mimics (n = 16) and age- and sex-matched healthy controls (n = 24) were profiled for non-coding RNA expression using RNA-sequencing, which showed a wide range of non-coding RNA to be dysregulated. We confirmed significant alterations with reverse transcription-quantitative PCR in the expression of hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-92a-3p, hsa-piR-33151, TRV-AAC4-1.1 and TRA-AGC6-1.1. Furthermore, hsa-miR-206, a previously identified amyotrophic lateral sclerosis biomarker, showed a binary-like pattern of expression in our samples. Using the expression of these non-coding RNA, we were able to discriminate amyotrophic lateral sclerosis samples from healthy controls in our discovery cohort using a random forest analysis with 93.7% accuracy with promise in predicting progression rate of patients. Importantly, cross-validation of this novel signature using a new geographically distinct cohort of samples from the United Kingdom and Germany with both amyotrophic lateral sclerosis and control samples (n = 156) yielded an accuracy of 73.9%. The high prediction accuracy of this non-coding RNA-based biomarker signature, even across heterogeneous cohorts, demonstrates the strength of our approach as a novel platform to identify and stratify amyotrophic lateral sclerosis patients. |
| first_indexed | 2024-03-06T23:41:58Z |
| format | Journal article |
| id | oxford-uuid:6f9fbc37-3a6c-46bd-a0e2-02ead145e19d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:41:58Z |
| publishDate | 2020 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:6f9fbc37-3a6c-46bd-a0e2-02ead145e19d2022-03-26T19:31:58ZIdentification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6f9fbc37-3a6c-46bd-a0e2-02ead145e19dEnglishSymplectic ElementsOxford University Press2020Joilin, GGray, EThompson, AGBobeva, YTalbot, KWeishaupt, JLudolph, AMalaspina, ALeigh, PNNewbury, SFTurner, MRHafezparast, MObjective biomarkers for the clinically heterogeneous adult-onset neurodegenerative disorder amyotrophic lateral sclerosis are crucial to facilitate assessing emerging therapeutics and improve the diagnostic pathway in what is a clinically heterogeneous syndrome. With non-coding RNA transcripts including microRNA, piwi-RNA and transfer RNA present in human biofluids, we sought to identify whether non-coding RNA in serum could be biomarkers for amyotrophic lateral sclerosis. Serum samples from our Oxford Study for Biomarkers in motor neurone disease/amyotrophic lateral sclerosis discovery cohort of amyotrophic lateral sclerosis patients (n = 48), disease mimics (n = 16) and age- and sex-matched healthy controls (n = 24) were profiled for non-coding RNA expression using RNA-sequencing, which showed a wide range of non-coding RNA to be dysregulated. We confirmed significant alterations with reverse transcription-quantitative PCR in the expression of hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-92a-3p, hsa-piR-33151, TRV-AAC4-1.1 and TRA-AGC6-1.1. Furthermore, hsa-miR-206, a previously identified amyotrophic lateral sclerosis biomarker, showed a binary-like pattern of expression in our samples. Using the expression of these non-coding RNA, we were able to discriminate amyotrophic lateral sclerosis samples from healthy controls in our discovery cohort using a random forest analysis with 93.7% accuracy with promise in predicting progression rate of patients. Importantly, cross-validation of this novel signature using a new geographically distinct cohort of samples from the United Kingdom and Germany with both amyotrophic lateral sclerosis and control samples (n = 156) yielded an accuracy of 73.9%. The high prediction accuracy of this non-coding RNA-based biomarker signature, even across heterogeneous cohorts, demonstrates the strength of our approach as a novel platform to identify and stratify amyotrophic lateral sclerosis patients. |
| spellingShingle | Joilin, G Gray, E Thompson, AG Bobeva, Y Talbot, K Weishaupt, J Ludolph, A Malaspina, A Leigh, PN Newbury, SF Turner, MR Hafezparast, M Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis |
| title | Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis |
| title_full | Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis |
| title_fullStr | Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis |
| title_full_unstemmed | Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis |
| title_short | Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis |
| title_sort | identification of a potential non coding rna biomarker signature for amyotrophic lateral sclerosis |
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