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Clustering of Alzheimer's and Parkinson's disease based on genetic burden of shared molecular mechanisms.

ABSTRACT: One of the visions of precision medicine has been to re-define disease taxonomies based on molecular characteristics rather than on phenotypic evidence. However, achieving this goal is highly challenging, specifically in neurology. Our contribution is a machine-learning based joint molecular subtyping of Alzheimer's (AD) and Parkinson's Disease (PD), based on the genetic burden of 15 molecular mechanisms comprising 27 proteins (e.g. APOE) that have been described in both diseases. We demonstrate that our joint AD/PD clustering using a combination of sparse autoencoders and sparse non-negative matrix factorization is reproducible and can be associated with significant differences of AD and PD patient subgroups on a clinical, pathophysiological and molecular level. Hence, clusters are disease-associated. To our knowledge this work is the first demonstration of a mechanism based stratification in the field of neurodegenerative diseases. Overall, we thus see this work as an important step towards a molecular mechanism-based taxonomy of neurological disorders, which could help in developing better targeted therapies in the future by going beyond classical phenotype based disease definitions.

SUBMITTER: Emon MA

PROVIDER: S-EPMC7645798 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Clustering of Alzheimer's and Parkinson's disease based on genetic burden of shared molecular mechanisms.

Emon Mohammad Asif MA Heinson Ashley A Wu Ping P Domingo-Fernández Daniel D Sood Meemansa M Vrooman Henri H Corvol Jean-Christophe JC Scordis Phil P Hofmann-Apitius Martin M Fröhlich Holger H

Scientific reports 20201105 1

One of the visions of precision medicine has been to re-define disease taxonomies based on molecular characteristics rather than on phenotypic evidence. However, achieving this goal is highly challenging, specifically in neurology. Our contribution is a machine-learning based joint molecular subtyping of Alzheimer's (AD) and Parkinson's Disease (PD), based on the genetic burden of 15 molecular mechanisms comprising 27 proteins (e.g. APOE) that have been described in both diseases. We demonstrate ...[more]

PMID: 33154531

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Dataset Information

Clustering of Alzheimer's and Parkinson's disease based on genetic burden of shared molecular mechanisms.

Publications

Clustering of Alzheimer's and Parkinson's disease based on genetic burden of shared molecular mechanisms.

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