{"doi":"10.3390/genes17050577","title":"Longitudinal Repeatome Remodeling in Peripheral Blood Following Parkinson’s Disease Diagnosis","abstract":"<jats:p>Background/Objectives: Parkinson’s disease (PD) is associated with systemic molecular alterations that extend beyond the central nervous system, including changes in peripheral blood transcriptomic profiles. While prior studies have focused predominantly on coding-gene expression, the longitudinal behavior of the peripheral blood repeatome following clinical diagnosis remains poorly characterized. Here, we investigated temporal remodeling of repetitive-element transcription over 36 months post-diagnosis by integrating repeat subfamily- and locus-specific analyses. Methods: Repeatome expression was quantified using SalmonTE and DESeq2 in peripheral blood RNA-seq data from 1560 PD and control individuals at diagnostic baseline (BL) and four follow-up visits (6, 12, 24, and 36 months). Differential expression was assessed at the subfamily level, with additional locus-specific validation in a representative subset. Results: A total of 259 repeat subfamilies were differentially expressed (padj &lt; 0.05), of which 224 (86.5%) were already detected at baseline. Enrichment of differential expression was significantly higher at baseline than at later visits (odds ratio = 30.9, p &lt; 2.2 × 10−16), with limited additional divergence over time. Longitudinal analyses revealed non-linear trajectories in selected repeat families, including Alu and SVA subfamilies. Locus-specific analysis identified 237 significantly regulated elements, demonstrating heterogeneous, site-specific transcriptional changes, including clusters of differentially expressed loci and instances within PD-relevant genomic regions (e.g., SNCA and IKZF2). Conclusions: Peripheral blood repeatome expression differs between PD and control groups, with the dominant signal established at clinical diagnosis and modest longitudinal modulation thereafter. Integration of locus-level analysis indicates that subfamily level patterns arise from discrete genomic events rather than uniform regulation. These findings support a model of systemic, immune-associated transcriptomic remodeling in circulating blood cells and position the peripheral repeatome as a dynamic framework for biomarker discovery and future mechanistic investigation.</jats:p>","journal":"Genes","year":2026,"id":643592,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":627958,"name":"Sulev Kõks","orcid":"0000-0001-6087-6643","position":1,"is_corresponding":false},{"id":1301116,"name":"Jerzy K. Kulski","orcid":"0000-0002-9789-245X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Longitudinal Repeatome Remodeling in Peripheral Blood Following Parkinson’s Disease Diagnosis","abstract":"<jats:p>Background/Objectives: Parkinson’s disease (PD) is associated with systemic molecular alterations that extend beyond the central nervous system, including changes in peripheral blood transcriptomic profiles. While prior studies have focused predominantly on coding-gene expression, the longitudinal behavior of the peripheral blood repeatome following clinical diagnosis remains poorly characterized. Here, we investigated temporal remodeling of repetitive-element transcription over 36 months post-diagnosis by integrating repeat subfamily- and locus-specific analyses. Methods: Repeatome expression was quantified using SalmonTE and DESeq2 in peripheral blood RNA-seq data from 1560 PD and control individuals at diagnostic baseline (BL) and four follow-up visits (6, 12, 24, and 36 months). Differential expression was assessed at the subfamily level, with additional locus-specific validation in a representative subset. Results: A total of 259 repeat subfamilies were differentially expressed (padj &lt; 0.05), of which 224 (86.5%) were already detected at baseline. Enrichment of differential expression was significantly higher at baseline than at later visits (odds ratio = 30.9, p &lt; 2.2 × 10−16), with limited additional divergence over time. Longitudinal analyses revealed non-linear trajectories in selected repeat families, including Alu and SVA subfamilies. Locus-specific analysis identified 237 significantly regulated elements, demonstrating heterogeneous, site-specific transcriptional changes, including clusters of differentially expressed loci and instances within PD-relevant genomic regions (e.g., SNCA and IKZF2). Conclusions: Peripheral blood repeatome expression differs between PD and control groups, with the dominant signal established at clinical diagnosis and modest longitudinal modulation thereafter. Integration of locus-level analysis indicates that subfamily level patterns arise from discrete genomic events rather than uniform regulation. These findings support a model of systemic, immune-associated transcriptomic remodeling in circulating blood cells and position the peripheral repeatome as a dynamic framework for biomarker discovery and future mechanistic investigation.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"42195038","pmcid":"PMC13206192","openalex_id":"https://openalex.org/W7161817194","authors":[],"funders":[{"funder_name":"The Multiple Sclerosis Society of Western Australia","grant_id":"032022","title":null},{"funder_name":"Michael J. Fox Foundation","grant_id":"18213","title":null},{"funder_name":"Perron Institute for Neurological and Translational Science","grant_id":"092018","title":null}],"total_grants":3,"fwci":0.0,"citation_percentile":0.60678068,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.3390/genes17050577","host_type":"journal"},{"url":"https://doi.org/10.3390/genes17050577","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4425/17/5/577/pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42195038","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13206192/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC13206192","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC13206192?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Parkinson's Disease Mechanisms and Treatments","Genetic Neurodegenerative Diseases","Lysosomal Storage Disorders Research"],"mesh_terms":["Aged","Female","Gene Expression Regulation","Humans","Longitudinal Studies","Male","Middle Aged","Parkinson Disease","Repetitive Sequences, Nucleic Acid","Biomarkers","Gene Expression Profiling","Transcriptome"],"keywords":["Transcriptome","Subfamily","Peripheral blood","Peripheral","Gene expression profiling","Longitudinal study","Gene expression","Disease","False discovery rate","Transposable elements","Parkinson disease","Immune regulation","Longitudinal Biomarkers","Repeatome","Peripheral Blood Repeat Transcriptomics","Small Rna Pseudogenes"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T17:53:41.282209Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}