CircRNA Biomarkers for Post-Infection Neurological Conditions

Background and Rationale

Post-infection long-term conditions represent a major unmet clinical need, with neurological manifestations among the most debilitating consequences. Cognitive dysfunction, neuroinflammation, and accelerated neurodegeneration following viral, bacterial, and parasitic infections remain poorly understood and lack reliable diagnostic tools. Long COVID alone affects millions with persistent brain fog, fatigue, and cognitive impairment, while other post-infectious syndromes (post-Lyme, post-sepsis encephalopathy) present similar challenges.

Circular RNAs (circRNAs) are emerging as ideal biomarkers for neurological conditions due to their exceptional stability in biofluids (resistant to exonuclease degradation), brain-enriched expression patterns, and disease-specific dysregulation. Their closed-loop structure makes them detectable in blood, CSF, and extracellular vesicles long after acute infection resolves, precisely when post-infection sequelae manifest.

Our group use computational pipelines for circRNA biomarker discovery, integrating multi-cohort RNA-seq data with machine learning approaches to identify robust diagnostic signatures. We seek to apply this expertise to the critical challenge of post-infection neurological conditions.

Expertise and Resources

Core Competencies

•       CircRNA bioinformatics: Specialised pipelines for circRNA detection, quantification, and functional annotation from RNA-seq data; ceRNA network construction; host gene interaction analysis

•       AI/ML for biomarkers: Feature selection algorithms, ensemble classifiers (e.g. Random Forest), cross-cohort validation strategies, multi-marker panel development

•       Multi-omics integration: Combined analysis of circRNA + miRNA + mRNA expression and m6A epitranscriptomic modifications for comprehensive biomarker signatures

•       Neuroepigenetics: Expertise in non-coding RNA biology (circRNAs, tRNA-derived fragments) and histone modifications in neuroinflammation and neurodegeneration

Experimental Capabilities

•       Neuronal and glial cultures for mechanistic validation

•       Mouse models of neuroinflammation and neurodegeneration

•       RNA isolation from diverse biofluids (plasma, CSF, extracellular vesicles)

•       RT-qPCR validation of candidate circRNA biomarkers

Track Record

•       Publications in Nature, EMBO Journal, PNAS on non-coding RNAs in brain disorders

•       Experience processing >800 RNA-seq samples for biomarker discovery

•       Established collaborations with clinical cohorts across Europe

Research Objectives in Proposed Project

•       Identify circRNA signatures associated with post-infection neurological sequelae through systematic analysis of patient cohorts vs. recovered controls

•       Develop AI-powered diagnostic panels integrating circRNAs with clinical and molecular variables for early detection and disease progression monitoring

•       Investigate circRNA-based mechanisms linking acute infection to long-term neurological dysfunction (neuroinflammation, blood-brain barrier integrity, glial activation)

•       Validate candidate biomarkers in independent cohorts and longitudinal samples

•       Contribute to understanding protective vs. risk factors through epigenetic and transcriptomic profiling

Contributions to Consortium

•       WP on Biomarker Discovery: Lead circRNA profiling and AI-based signature development from consortium samples

•       Bioinformatics support: Provide computational pipelines, data integration, and machine learning expertise across work packages

•       Mechanistic validation: Functional studies in cellular and animal models to validate biomarker candidates