Shouq Kaaki

تخصص المعلوماتية الحيوية · دفعة 2025

Unveiling Alternative Splicing Isoforms as Candidate Biomarkers for the Diagnosis of Major Depressive Disorder

This project investigated alternative splicing isoforms as candidate biomarkers for Major Depressive Disorder (MDD). Peripheral blood RNA from MDD patients and controls was analyzed using the nf-core/rnasplice pipeline, with splicing events quantified by rMATS v2.10. Isoforms were first filtered based on false discovery rate (FDR) and percent spliced-in (PSI), using read counts only as a minimum threshold to ensure reliability. Differential analysis revealed that skipped exons were the most abundant significant events, while retained introns were enriched in DNA repair–related genes. Since no single isoform fully separated cases from controls, a LASSO-regularized logistic regression model (glmnet) was applied to identify a diagnostic multi-isoform panel. Enrichment of glmnet-selected features highlighted pathways involved in apoptosis, telomere maintenance, synaptic development and plasticity, cell cycle regulation, and neuronal survival, all processes previously implicated in MDD pathophysiology. The purpose of this trial is to establish whether splicing-derived isoform panels can serve as objective biomarkers for MDD diagnosis, to be used alongside the DSM-IV framework after confirmation in clinical trials. By improving diagnostic accuracy, this approach also aims to address the likelihood that depression represents a spectrum of molecular subtypes, an idea supported by contradictory findings in the literature on disease mechanisms.

المشرف: Hugo Tavares, Andries van Tonder

اقرأ التقرير النهائي (PDF)

اطّلع عليه في تقرير البرنامج (PDF)