Peripheral blood MicroRNAs as biomarkers of schizophrenia: expectations from a meta-analysis that combines deep learning methods

Objectives: This study aimed at identifying reliable differentially expressed miRNAs (DEMs) for schizophrenia in blood via meta-analyses combined with deep learning methods. Methods: First, we meta-analysed published DEMs. Then, we enriched the pool of schizophrenia-associated miRNAs by applying two computational learning methods to identify candidate biomarkers and verified the results in external datasets. Results: In total, 27 DEMs were found to be statistically significant (p<.05). Ten candidate schizophrenia-associated miRNAs were identified through computational learning methods. The diagnostic efficiency was verified on a blood-miRNA dataset (GSE54578) with a random forest (RF) model and achieved an area under the curve (AUC) of 0.83 +/- 0.14. Moreover, 855 experimentally validated target genes for these candidate miRNAs were retrieved, and 11 hub genes were identified. Enrichment analysis revealed that the main functions in which the target genes were enriched were those related to cell signalling, prenatal infections, cancers, cell deaths, oxidative stress, endocrine disorders, transcription regulation, and kinase activities. The diagnostic ability of the hub genes was reflected in a comparably good average AUC of 0.77 +/- 0.09 for an external dataset (GSE38484). Conclusions: A meta-analysis that combines computational and mathematical methods provides a reliable tool for identifying candidate biomarkers of schizophrenia.

Automated summary

This study used meta-analyses and deep learning methods to identify reliable differentially expressed miRNAs (DEMs) for schizophrenia in blood. Computational learning methods were used to enrich the pool of schizophrenia-associated miRNAs and identify candidate biomarkers. The diagnostic efficiency of the identified miRNAs and hub genes was verified and showed promising results. This research provides a reliable tool for identifying candidate biomarkers of schizophrenia.