Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson’s disease progression

Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson’s disease progression. Kern, F., Fehlmann, T., Violich, I., Alsop, E., Hutchins, E., Kahraman, M., Grammes, N., Guimarães, P., Backes, C., Poston, K., Casey, B., Balling, R., Geffers, L., Krüger, R., Galasko, D., Mollenhauer, B., Meese, E., Wyss-Coray, T., Craig, D., Keuren-Jensen, K. V., & Keller, A. Nature Aging, 1:309-322, 03, 2021.

Paper doi abstract bibtex 5 downloads

Noncoding RNAs have diagnostic and prognostic importance in Parkinson’s disease (PD). We studied circulating small noncoding RNAs (sncRNAs) in two large-scale longitudinal PD cohorts (Parkinson’s Progression Markers Initiative (PPMI) and Luxembourg Parkinson’s Study (NCER-PD)) and modeled their impact on the transcriptome. Sequencing of sncRNAs in 5,450 blood samples of 1,614 individuals in PPMI yielded 323 billion reads, most of which mapped to microRNAs but covered also other RNA classes such as piwi-interacting RNAs, ribosomal RNAs and small nucleolar RNAs. Dysregulated microRNAs associated with disease and disease progression occur in two distinct waves in the third and seventh decade of life. Originating predominantly from immune cells, they resemble a systemic inflammation response and mitochondrial dysfunction, two hallmarks of PD. Profiling 1,553 samples from 1,024 individuals in the NCER-PD cohort validated biomarkers and main findings by an independent technology. Finally, network analysis of sncRNA and transcriptome sequencing from PPMI identified regulatory modules emerging in patients with progressing PD. The authors present a small noncoding RNA atlas characterizing two longitudinal Parkinson’s disease cohorts and reveal potential biomarkers for disease detection, their relation to molecular hallmarks of PD and regulatory disease-progression modules.

@article{kern2131,
	author = {Kern, Fabian and Fehlmann, Tobias and Violich, Ivo and Alsop, Eric and Hutchins, Elizabeth and Kahraman, Mustafa and Grammes, Nadja and Guimarães, Pedro and Backes, Christina and Poston, Kathleen and Casey, Bradford and Balling, Rudi and Geffers, Lars and Krüger, Rejko and Galasko, Douglas and Mollenhauer, Brit and Meese, Eckart and Wyss-Coray, Tony and Craig, David and Keuren-Jensen, Kendall Van  and Keller, Andreas},
	year = {2021},
	month = {03},
	pages = {309-322},
	title = {Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson’s disease progression},
	abstract = {Noncoding RNAs have diagnostic and prognostic importance in Parkinson’s disease (PD). We studied circulating small noncoding RNAs (sncRNAs) in two large-scale longitudinal PD cohorts (Parkinson’s Progression Markers Initiative (PPMI) and Luxembourg Parkinson’s Study (NCER-PD)) and modeled their impact on the transcriptome. Sequencing of sncRNAs in 5,450 blood samples of 1,614 individuals in PPMI yielded 323 billion reads, most of which mapped to microRNAs but covered also other RNA classes such as piwi-interacting RNAs, ribosomal RNAs and small nucleolar RNAs. Dysregulated microRNAs associated with disease and disease progression occur in two distinct waves in the third and seventh decade of life. Originating predominantly from immune cells, they resemble a systemic inflammation response and mitochondrial dysfunction, two hallmarks of PD. Profiling 1,553 samples from 1,024 individuals in the NCER-PD cohort validated biomarkers and main findings by an independent technology. Finally, network analysis of sncRNA and transcriptome sequencing from PPMI identified regulatory modules emerging in patients with progressing PD. The authors present a small noncoding RNA atlas characterizing two longitudinal Parkinson’s disease cohorts and reveal potential biomarkers for disease detection, their relation to molecular hallmarks of PD and regulatory disease-progression modules.},
	volume = {1},
	journal = {Nature Aging},
	doi = {10.1038/s43587-021-00042-6},
	URL = {https://www.nature.com/articles/s43587-021-00042-6}
}

Downloads: 5