4.6 Article

Personalized Protein-Protein Interaction Networks Towards Unraveling the Molecular Mechanisms of Alzheimer's Disease

Journal

MOLECULAR NEUROBIOLOGY
Volume -, Issue -, Pages -

Publisher

SPRINGER
DOI: 10.1007/s12035-023-03690-4

Keywords

Alzheimer's disease; Subnetwork discovery; Personalized networks; Transcriptome data; Disease subtypes; Protein-protein interaction

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This study adopted a personalized approach to analyze transcriptome data from 403 patients with Alzheimer's disease (AD) and discovered several affected pathways that were consistent with suggested AD subtypes.
Alzheimer's disease (AD) is a highly heterogenous neurodegenerative disease, and several omic-based datasets were generated in the last decade from the patients with the disease. However, the vast majority of studies evaluate these datasets in bulk by considering all the patients as a single group, which obscures the molecular differences resulting from the heterogeneous nature of the disease. In this study, we adopted a personalized approach and analyzed the transcriptome data from 403 patients individually by mapping the data on a human protein-protein interaction network. Patient-specific subnetworks were discovered and analyzed in terms of the genes in the subnetworks, enriched functional terms, and known AD genes. We identified several affected pathways that could not be captured by the bulk comparison. We also showed that our personalized findings point to patterns of alterations consistent with the recently suggested AD subtypes.

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