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Deep sncRNA-seq of the PPMI cohort to study Parkinson’s disease progression
Kern, Fabian; Fehlmann, Tobias; Violich, Ivo et al.


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Keywords :
RNAs; Parkinson’s diseases; sncRNA-seq
Abstract :
[en] Coding and non-coding RNAs have diagnostic and prognostic importance in Parkinson’s diseases (PD). We studied circulating small non-coding RNAs (sncRNAs) in 7, 003 samples from two longitudinal PD cohorts (Parkinson’s Progression Marker Initiative (PPMI) and Luxembourg Parkinson’s Study (NCER-PD)) and modelled their influence on the transcriptome. First, we sequenced sncRNAs in 5, 450 blood samples of 1, 614 individuals in PPMI. The majority of 323 billion reads (59 million reads per sample) mapped to miRNAs. Other covered RNA classes include piRNAs, rRNAs, snoRNAs, tRNAs, scaRNAs, and snRNAs. De-regulated miRNAs were associated with the disease and disease progression and occur in two distinct waves in the third and seventh decade of live. Originating mostly from a characteristic set of immune cells they resemble a systemic inflammation response and mitochondrial dysfunction, two hallmarks of PD. By profiling 1, 553 samples from 1, 024 individuals in the NCER-PD cohort using an independent technology, we validate relevant findings from the sequencing study. Finally, network analysis of sncRNAs and transcriptome sequencing of the original cohort identified regulatory modules emerging in progressing PD patients.Competing Interest StatementThe authors have declared no competing interest.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kern, Fabian;  Saarland University > Clinical Bioinformatics
Fehlmann, Tobias;  Saarland University > Clinical Bioinformatics
Violich, Ivo;  University of Southern California > Keck School of Medicine
Alsop, Eric;  Translational Genomics Research Institute > Neurogenomics Division
Hutchins, Elizabeth;  Translational Genomics Research Institute > Neurogenomics Division
Kahraman, Mustafa
Grammes, Nadja Liddy
Guimarães, Pedro
Backes, Christina
Poston, Kathleen
Casey, Bradford
Balling, Rudolf ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Geffers, Lars ;  Luxembourg Institute of Health - LIH
Krüger, Rejko ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Galasko, Douglas
Mollenhauer, Brit
Meese, Eckart
Wyss-Coray, Tony
Craig, David Wesley
Van Keuren-Jensen, Kendall
Keller, Andreas
More authors (11 more) Less
Language :
Title :
Deep sncRNA-seq of the PPMI cohort to study Parkinson’s disease progression
Publication date :
01 June 2020
Publisher :
Cold Spring Harbor Laboratory
Focus Area :
Systems Biomedicine
Funders :
Michael J. Fox Foundation


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