Integrated Systems Analysis Explores Dysfunctional Molecular Modules and Regulatory Factors in Children with Autism Spectrum Disorder.
J Mol Neurosci
; 71(2): 358-368, 2021 Feb.
Article
em En
| MEDLINE
| ID: mdl-32653993
ABSTRACT
Autism spectrum disorder (ASD) is a genetic neurodevelopmental disorder involving multiple genes that occurs in early childhood, and a number of risk genes have been reported in previous studies. However, the molecular mechanism of the polygenic regulation leading to pathological changes in ASD remains unclear. First, we identified 8 dysregulated gene coexpression modules by analyzing blood transcriptome data from 96 children with ASD and 42 controls. These modules are rich in ASD risk genes and function related to metabolism, immunity, neurodevelopment, and signaling. The regulatory factors of each module including microRNA (miRNA) and transcription factors (TFs) were subsequently predicted based on transcriptional and posttranscriptional regulation. We identified a set of miRNAs that regulate metabolic and immune modules, as well as transcription factors that cause dysregulation of the modules, and we constructed a coregulatory network between the regulatory factors and modules. Our work reveals dysfunctional modules in children with ASD, elucidates the role of miRNA and transcription factor dysregulation in the pathophysiology of ASD, and helps us to further understand the underlying molecular mechanism of ASD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Redes Reguladoras de Genes
/
Transtorno do Espectro Autista
Tipo de estudo:
Prognostic_studies
Limite:
Child
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article