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Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale.
Cells. 2020 12 08; 9(12)C

Abstract

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies have suggested relations between neurodegenerative diseases for many years (e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways). We gathered publicly available genomic, transcriptomic, and proteomic data from 177 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases on three analyzed omics-layers. The results show a remarkably high number of shared differentially expressed genes between the transcriptomic and proteomic levels for all conditions, while showing a significant relation between genomic and proteomic data between AD and PD and AD and ALS. We identified a set of 139 genes being differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented gene ontology (GO) Terms involved in the development of neurodegeneration, such as response to heat and hypoxia, positive regulation of cytokines and angiogenesis, and RNA catabolic process. Furthermore, the four analyzed neurodegenerative diseases (NDDs) were clustered by their mean direction of regulation throughout all transcriptomic studies for this set of 139 genes, with the closest relation regarding this common gene set seen between AD and HD. GO-Term and pathway analysis of the proteomic overlap led to biological processes (BPs), related to protein folding and humoral immune response. Taken together, we could confirm the existence of many relations between Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis on transcriptomic and proteomic levels by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection and the striking relation of the results to processes leading to neurodegeneration between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring many studies simultaneously, including multiple omics-layers of different neurodegenerative diseases simultaneously, holds new relevant insights that do not emerge from analyzing these data separately. Furthermore, the results shed light on processes like the humoral immune response that have previously been described only for certain diseases. Our data therefore suggest human patients with neurodegenerative diseases should be addressed as complex biological systems by integrating multiple underlying data sources.

Authors+Show Affiliations

Institute for Human Genetics, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany. Leibniz Institute for Resilience Research, Leibniz Association, Wallstraβe 7, 55122 Mainz, Germany.Institute for Human Genetics, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.Institute for Human Genetics, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.Institute for Human Genetics, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33302607

Citation

Ruffini, Nicolas, et al. "Common Factors in Neurodegeneration: a Meta-Study Revealing Shared Patterns On a Multi-Omics Scale." Cells, vol. 9, no. 12, 2020.
Ruffini N, Klingenberg S, Schweiger S, et al. Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale. Cells. 2020;9(12).
Ruffini, N., Klingenberg, S., Schweiger, S., & Gerber, S. (2020). Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale. Cells, 9(12). https://doi.org/10.3390/cells9122642
Ruffini N, et al. Common Factors in Neurodegeneration: a Meta-Study Revealing Shared Patterns On a Multi-Omics Scale. Cells. 2020 12 8;9(12) PubMed PMID: 33302607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale. AU - Ruffini,Nicolas, AU - Klingenberg,Susanne, AU - Schweiger,Susann, AU - Gerber,Susanne, Y1 - 2020/12/08/ PY - 2020/10/16/received PY - 2020/11/24/revised PY - 2020/12/04/accepted PY - 2020/12/11/entrez PY - 2020/12/12/pubmed PY - 2021/6/22/medline KW - Alzheimer’s disease KW - Huntington’s disease KW - Parkinson’s disease KW - amyotrophic lateral sclerosis KW - multi-omics KW - neurodegeneration JF - Cells JO - Cells VL - 9 IS - 12 N2 - Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies have suggested relations between neurodegenerative diseases for many years (e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways). We gathered publicly available genomic, transcriptomic, and proteomic data from 177 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases on three analyzed omics-layers. The results show a remarkably high number of shared differentially expressed genes between the transcriptomic and proteomic levels for all conditions, while showing a significant relation between genomic and proteomic data between AD and PD and AD and ALS. We identified a set of 139 genes being differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented gene ontology (GO) Terms involved in the development of neurodegeneration, such as response to heat and hypoxia, positive regulation of cytokines and angiogenesis, and RNA catabolic process. Furthermore, the four analyzed neurodegenerative diseases (NDDs) were clustered by their mean direction of regulation throughout all transcriptomic studies for this set of 139 genes, with the closest relation regarding this common gene set seen between AD and HD. GO-Term and pathway analysis of the proteomic overlap led to biological processes (BPs), related to protein folding and humoral immune response. Taken together, we could confirm the existence of many relations between Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis on transcriptomic and proteomic levels by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection and the striking relation of the results to processes leading to neurodegeneration between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring many studies simultaneously, including multiple omics-layers of different neurodegenerative diseases simultaneously, holds new relevant insights that do not emerge from analyzing these data separately. Furthermore, the results shed light on processes like the humoral immune response that have previously been described only for certain diseases. Our data therefore suggest human patients with neurodegenerative diseases should be addressed as complex biological systems by integrating multiple underlying data sources. SN - 2073-4409 UR - https://www.unboundmedicine.com/medline/citation/33302607/Common_Factors_in_Neurodegeneration:_A_Meta_Study_Revealing_Shared_Patterns_on_a_Multi_Omics_Scale_ L2 - https://www.mdpi.com/resolver?pii=cells9122642 DB - PRIME DP - Unbound Medicine ER -