A Bioinformatic Study of Genetics Involved in Determining Mild Traumatic Brain Injury Severity and Recovery

TL;DR

This study identifies genes and miRNAs linked to mild traumatic brain injury severity and recovery, suggesting potential biomarkers for diagnosis.

Contribution

The study identifies novel hub genes and miRNAs associated with mTBI outcomes using bioinformatic analysis of public datasets.

Findings

Eleven hub genes (e.g., APOE, S100B) were linked to mTBI outcomes and neuronal regeneration pathways.

Eight miRNAs (e.g., hsa-miR-10a-5p) were associated with mTBI candidate genes and injury-related changes.

RNA sequencing revealed 2664 differentially expressed miRNAs post-mTBI, with some correlated to head impact.

Abstract

Objectives: This in silico study sought to identify specific biomarkers for mild traumatic brain injury (mTBI) through the analysis of publicly available gene and miRNA databases, hypothesizing their influence on neuronal structure, axonal integrity, and regeneration. Methods: This study implemented a three-step process: (1) data searching for mTBI-related genes in Gene and MalaCard databases and literature review, (2) data analysis involved performing functional annotation through GO and KEGG, identifying hub genes using Cytoscape, mapping protein–protein interactions via DAVID and STRING, and predicting miRNA targets using miRSystem, miRWalk2.0, and mirDIP, and (3) RNA-sequencing analysis applied to the mTBI dataset GSE123336. Results: Eleven candidate hub genes associated with mTBI outcome were identified: APOE, S100B, GFAP, BDNF, AQP4, COMT, MBP, UCHL1, DRD2, ASIC1, and CACNA1A. Enrichment analysis linked these genes to neuron projection regeneration and synaptic plasticity. miRNAs linked to the mTBI candidate genes were hsa-miR-9-5p, hsa-miR-204-5p, hsa-miR-1908-5p, hsa-miR-16-5p, hsa-miR-10a-5p, has-miR-218-5p, has-miR-34a-5p, and has-miR-199b-5p. The RNA sequencing revealed 2664 differentially expressed miRNAs post-mTBI, with 17 showing significant changes at the time of injury and 48 h post-injury. Two miRNAs were positively correlated with direct head hits. Conclusions: Our bioinformatic analysis suggests that specific genes and miRNAs, particularly hsa-miR-10a-5p, may be involved in molecular pathways influencing mTBI outcomes. Our research may guide future mTBI diagnostics, emphasizing the need to measure and track these specific genes and miRNAs in diverse cohorts.

Figures