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Prediction of differentially expressed microRNAs in blood as potential biomarkers for Alzheimer’s disease by meta-analysis and adaptive boosting ensemble learning
Yuen, Sze Chung1; Liang, Xiaonan1; Zhu, Hongmei1; Jia, Yongliang1,2,3; Leung, Siu wai4,5
2021-12-01
Source PublicationAlzheimers Research & Therapy
ISSN1758-9193
Volume13Issue:1Pages:126
Abstract

Background: Blood circulating microRNAs that are specific for Alzheimer’s disease (AD) can be identified from differentially expressed microRNAs (DEmiRNAs). However, non-reproducible and inconsistent reports of DEmiRNAs hinder biomarker development. The most reliable DEmiRNAs can be identified by meta-analysis. To enrich the pool of DEmiRNAs for potential AD biomarkers, we used a machine learning method called adaptive boosting for miRNA disease association (ABMDA) to identify eligible candidates that share similar characteristics with the DEmiRNAs identified from meta-analysis. This study aimed to identify blood circulating DEmiRNAs as potential AD biomarkers by augmenting meta-analysis with the ABMDA ensemble learning method. Methods: Studies on DEmiRNAs and their dysregulation states were corroborated with one another by meta-analysis based on a random-effects model. DEmiRNAs identified by meta-analysis were collected as positive examples of miRNA–AD pairs for ABMDA ensemble learning. ABMDA identified similar DEmiRNAs according to a set of predefined criteria. The biological significance of all resulting DEmiRNAs was determined by their target genes according to pathway enrichment analyses. The target genes common to both meta-analysis- and ABMDA-identified DEmiRNAs were collected to construct a network to investigate their biological functions. Results: A systematic database search found 7841 studies for an extensive meta-analysis, covering 54 independent comparisons of 47 differential miRNA expression studies, and identified 18 reliable DEmiRNAs. ABMDA ensemble learning was conducted based on the meta-analysis results and the Human MicroRNA Disease Database, which identified 10 additional AD-related DEmiRNAs. These 28 DEmiRNAs and their dysregulated pathways were related to neuroinflammation. The dysregulated pathway related to neuronal cell cycle re-entry (CCR) was the only statistically significant pathway of the ABMDA-identified DEmiRNAs. In the biological network constructed from 1865 common target genes of the identified DEmiRNAs, the multiple core ubiquitin-proteasome system, that is involved in neuroinflammation and CCR, was highly connected. Conclusion: This study identified 28 DEmiRNAs as potential AD biomarkers in blood, by meta-analysis and ABMDA ensemble learning in tandem. The DEmiRNAs identified by meta-analysis and ABMDA were significantly related to neuroinflammation, and the ABMDA-identified DEmiRNAs were related to neuronal CCR.

KeywordAbmda Alzheimer’s Disease Biomarkers Meta-analysis Micrornas Neuroinflammation Neuronal Cell Cycle Re-entry
DOI10.1186/s13195-021-00862-z
URLView the original
Indexed BySCIE ; SSCI
Language英語English
WOS Research AreaNeurosciences & Neurology
WOS SubjectClinical Neurology ; Neurosciences
WOS IDWOS:000671561400001
PublisherBMC, CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Scopus ID2-s2.0-85109605942
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Co-First AuthorYuen, Sze Chung
Corresponding AuthorLeung, Siu wai
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Avenida da Universidade, 999078, Macao
2.BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
3.Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4.Shenzhen Institute of Artificial Intelligence and Robotics for Society, Shenzhen, China
5.Edinburgh Bayes Centre for AI Research in Shenzhen, College of Science and Engineering, University of Edinburgh, Edinburgh, United Kingdom
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yuen, Sze Chung,Liang, Xiaonan,Zhu, Hongmei,et al. Prediction of differentially expressed microRNAs in blood as potential biomarkers for Alzheimer’s disease by meta-analysis and adaptive boosting ensemble learning[J]. Alzheimers Research & Therapy, 2021, 13(1), 126.
APA Yuen, Sze Chung., Liang, Xiaonan., Zhu, Hongmei., Jia, Yongliang., & Leung, Siu wai (2021). Prediction of differentially expressed microRNAs in blood as potential biomarkers for Alzheimer’s disease by meta-analysis and adaptive boosting ensemble learning. Alzheimers Research & Therapy, 13(1), 126.
MLA Yuen, Sze Chung,et al."Prediction of differentially expressed microRNAs in blood as potential biomarkers for Alzheimer’s disease by meta-analysis and adaptive boosting ensemble learning".Alzheimers Research & Therapy 13.1(2021):126.
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