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Journal article
Erosion of Gene Co-expression Networks Reveal Deregulation of Immune System Processes in Late-Onset Alzheimer’s Disease
Frontiers in neuroscience, v 14, 228
20 Mar 2020
PMID: 32265636
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We have applied a novel and integrative analysis framework for next-generation sequencing (NGS) data to 503 human subjects provided by the Religious Orders Study and Memory and Aging Project (ROSMAP) to examine changes in transcriptomic organization and common variants in association with late-onset Alzheimer’s disease (LOAD). Our framework identified seven reproducible, co-regulated modules after quality control (QC), clinical segregation, preservation filtering, and functional ontology analysis. These modules were specifically enriched in several innate and adaptive immune system processes, the synaptic vesicle cycle, and Hippo signaling. Topological and functional erosion of these modules due to shedding of genes and loss of in-module connectivity was diagnostic of disease progression. Perturbation analysis revealed that only 1% of eQTLs overlapped genes participating in these co-regulated modules. Common variants nevertheless identified components of the immune systems like human leukocyte antigen (HLA) complex and microtubule-associated protein tau (MAPT) regions in association with LOAD. Our results implicate microglial function, adaptive immune response, and the structural degeneration of neurons as contributors to the transcriptional deregulation observed along with common genetic variants in the progression of LOAD.
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Details
- Title
- Erosion of Gene Co-expression Networks Reveal Deregulation of Immune System Processes in Late-Onset Alzheimer’s Disease
- Creators
- John Stephen Malamon - Drexel UniversityAndres Kriete (Corresponding Author) - Drexel University
- Publication Details
- Frontiers in neuroscience, v 14, 228
- Publisher
- Frontiers Media S.A
- Number of pages
- 11
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000523478600001
- Scopus ID
- 2-s2.0-85083212405
- Other Identifier
- 991019168360604721
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- Web of Science research areas
- Neurosciences