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Deciphering cellular transcriptional alterations in Alzheimer’s disease brains
- Source :
- Molecular Neurodegeneration, Vol 15, Iss 1, Pp 1-15 (2020), Molecular Neurodegeneration
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- Large-scale brain bulk-RNAseq studies identified molecular pathways implicated in Alzheimer’s disease (AD), however these findings can be confounded by cellular composition changes in bulk-tissue. To identify cell intrinsic gene expression alterations of individual cell types, we designed a bioinformatics pipeline and analyzed three AD and control bulk-RNAseq datasets of temporal and dorsolateral prefrontal cortex from 685 brain samples. We detected cell-proportion changes in AD brains that are robustly replicable across the three independently assessed cohorts. We applied three different algorithms including our in-house algorithm to identify cell intrinsic differentially expressed genes in individual cell types (CI-DEGs). We assessed the performance of all algorithms by comparison to single nucleus RNAseq data. We identified consensus CI-DEGs that are common to multiple brain regions. Despite significant overlap between consensus CI-DEGs and bulk-DEGs, many CI-DEGs were absent from bulk-DEGs. Consensus CI-DEGs and their enriched GO terms include genes and pathways previously implicated in AD or neurodegeneration, as well as novel ones. We demonstrated that the detection of CI-DEGs through computational deconvolution methods is promising and highlight remaining challenges. These findings provide novel insights into cell-intrinsic transcriptional changes of individual cell types in AD and may refine discovery and modeling of molecular targets that drive this complex disease.
- Subjects :
- 0301 basic medicine
Cell type
genetic structures
Bioinformatics
Cell
Disease
Computational biology
Deconvolution
Biology
lcsh:Geriatrics
lcsh:RC346-429
Transcriptome
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Alzheimer Disease
Gene expression
medicine
Humans
Neurodegeneration
Molecular Biology
Gene
lcsh:Neurology. Diseases of the nervous system
030304 developmental biology
Cell-specific gene expression
0303 health sciences
Gene Expression Profiling
Brain
Computational Biology
RNA sequencing
medicine.disease
Molecular medicine
Dorsolateral prefrontal cortex
lcsh:RC952-954.6
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Neurology (clinical)
sense organs
Nucleus
Alzheimer’s disease
030217 neurology & neurosurgery
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 17501326
- Volume :
- 15
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Neurodegeneration
- Accession number :
- edsair.doi.dedup.....8f35c8dda98dd3a97de940bde16a4043