Logo image
Back
A whole-transcriptome analysis of differentially expressed genes, transcripts, and transcript usage in blood samples from Parkinson’s disease patients
Journal article   Open access   Peer reviewed

A whole-transcriptome analysis of differentially expressed genes, transcripts, and transcript usage in blood samples from Parkinson’s disease patients

Sulev Koks, Sulev Koks, Mari Muldmaa, Mari Muldmaa, Jack Price, Luke Whiley, Luke Whiley, Luke Whiley, Luke Whiley, Maili Jakobson, …
Experimental biology and medicine (Maywood, N.J.), Vol.251
2026
DOI: https://doi.org/10.3389/ebm.2026.11099
pdf
transriptome4.13 MBDownloadView
Open Access CC BY V4.0

Abstract

alternative splicing biomarkers gene expression profiling Parkinson’s disease RNA-seq
Parkinson’s disease (PD) is a complex neurodegenerative disorder with diverse molecular signatures that extend beyond the central nervous system. Peripheral blood serves as a minimally invasive source of transcriptomic biomarkers reflecting systemic inflammation, mitochondrial dysfunction, lysosomal impairment, and disrupted RNA processing—key pathways involved in PD. Long-read RNA sequencing with Oxford Nanopore Technologies (ONT) offers unprecedented detail of full-length transcripts, alternative isoforms, and RNA modifications, enabling more accurate detection of disease-related transcriptional changes. We conducted high-throughput ONT long-read RNA sequencing on blood samples from 145 individuals, including PD patients and age-matched healthy controls. RNA libraries were prepared using a cDNA-based protocol optimised for high-accuracy PromethION sequencing. Transcriptomes were quantified with ONT-specific pipelines, and analyses of differential gene expression (DGE), differential transcript expression (DEX), differential transcript usage (DTU), and alternative splicing were performed using ONT-aware tools such as DRIMSeq, DEXSeq, and stageR. Pathway enrichment linked disease-related changes to mitochondrial, lysosomal, and vesicle-trafficking pathways. Our analysis identified highly significant PD-associated transcriptional signatures in peripheral blood (SNCA, VPS13C, LRRK2, GRN, STAU1, NPTN, PARK7). Long-read sequencing uncovered extensive isoform-level dysregulation, including novel transcript variants (e.g., BCL2L2-PABPN1, SQSTM1) in pathways relevant to PD, such as autophagy and endolysosomal trafficking. DTU analyses revealed shifts in isoforms of LRRK2 and GBA1, indicating widespread disturbances in RNA processing. Enrichment analysis showed activation of molecular pathways linked to neurodegeneration. This study provides the largest long-read blood transcriptomic dataset in PD to date, demonstrating that ONT sequencing can resolve isoform-level changes and reveal systemic molecular signatures of PD. Our findings support the development of blood-based RNA biomarkers and the establishment of long-read transcriptomics as a transformative approach for genomic pathology in PD.

Details

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

Source: SDGs in the Output

Metrics

1 Record Views
Logo image