Dataset Information

Cell type characterization of spatiotemporal gene co-expression modules in Down syndrome brain.

ABSTRACT: Down syndrome (DS) is the most common genetic cause of intellectual disability and increases the risk of other brain-related dysfunctions, like seizures, early-onset Alzheimer's disease, and autism. To reveal the molecular profiles of DS-associated brain phenotypes, we performed a meta-data analysis of the developmental DS brain transcriptome at cell type and co-expression module levels. In the DS brain, astrocyte-, microglia-, and endothelial cell-associated genes show upregulated patterns, whereas neuron- and oligodendrocyte-associated genes show downregulated patterns. Weighted gene co-expression network analysis identified cell type-enriched co-expressed gene modules. We present eight representative cell-type modules for neurons, astrocytes, oligodendrocytes, and microglia. We classified the neuron modules into glutamatergic and GABAergic neurons and associated them with detailed subtypes. Cell type modules were interpreted by analyzing spatiotemporal expression patterns, functional annotations, and co-expression networks of the modules. This study provides insight into the mechanisms underlying brain abnormalities in DS and related disorders.

SUBMITTER: Seol S

PROVIDER: S-EPMC9840153 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Cell type characterization of spatiotemporal gene co-expression modules in Down syndrome brain.

Seol Sihwan S Kwon Joonhong J Kang Hyo Jung HJ

iScience 20221228 1

Down syndrome (DS) is the most common genetic cause of intellectual disability and increases the risk of other brain-related dysfunctions, like seizures, early-onset Alzheimer's disease, and autism. To reveal the molecular profiles of DS-associated brain phenotypes, we performed a meta-data analysis of the developmental DS brain transcriptome at cell type and co-expression module levels. In the DS brain, astrocyte-, microglia-, and endothelial cell-associated genes show upregulated patterns, whe ...[more]

PMID: 36647384

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Project description:BACKGROUND: Biological networks characterize the interactions of biomolecules at a systems-level. One important property of biological networks is the modular structure, in which nodes are densely connected with each other, but between which there are only sparse connections. In this report, we attempted to find the relationship between the network topology and formation of modular structure by comparing gene co-expression networks with random networks. The organization of gene functional modules was also investigated. RESULTS: We constructed a genome-wide Arabidopsis gene co-expression network (AGCN) by using 1094 microarrays. We then analyzed the topological properties of AGCN and partitioned the network into modules by using an efficient graph clustering algorithm. In the AGCN, 382 hub genes formed a clique, and they were densely connected only to a small subset of the network. At the module level, the network clustering results provide a systems-level understanding of the gene modules that coordinate multiple biological processes to carry out specific biological functions. For instance, the photosynthesis module in AGCN involves a very large number (> 1000) of genes which participate in various biological processes including photosynthesis, electron transport, pigment metabolism, chloroplast organization and biogenesis, cofactor metabolism, protein biosynthesis, and vitamin metabolism. The cell cycle module orchestrated the coordinated expression of hundreds of genes involved in cell cycle, DNA metabolism, and cytoskeleton organization and biogenesis. We also compared the AGCN constructed in this study with a graphical Gaussian model (GGM) based Arabidopsis gene network. The photosynthesis, protein biosynthesis, and cell cycle modules identified from the GGM network had much smaller module sizes compared with the modules found in the AGCN, respectively. CONCLUSION: This study reveals new insight into the topological properties of biological networks. The preferential hub-hub connections might be necessary for the formation of modular structure in gene co-expression networks. The study also reveals new insight into the organization of gene functional modules.

Dataset Information

Cell type characterization of spatiotemporal gene co-expression modules in Down syndrome brain.

Publications

Cell type characterization of spatiotemporal gene co-expression modules in Down syndrome brain.

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