- Huan Gao1,
- Jiayong Zhong1,
- Qingsheng Huang1,
- Xiaohui Wu1,
- Xueying Mo2,
- Long Lu1,2,3 &
- …
- Huiying Liang ORCID:orcid.org/0000-0002-9987-80021
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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.
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Acknowledgments
We also thank the data providers Kong SW et al. and Gregg JP et al.
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This work was supported by Guangzhou Institute of Pediatrics/Guangzhou Women and Children’s Medical Center (YIP-2019-026).
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Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Guangzhou, 510623, Guangdong, China
Huan Gao, Jiayong Zhong, Qingsheng Huang, Xiaohui Wu, Long Lu & Huiying Liang
School of Information Management, Wuhan University, Wuhan, 430072, Hubei, China
Xueying Mo & Long Lu
Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA
Long Lu
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Gao, H., Zhong, J., Huang, Q.et al. Integrated Systems Analysis Explores Dysfunctional Molecular Modules and Regulatory Factors in Children with Autism Spectrum Disorder.J Mol Neurosci71, 358–368 (2021). https://doi.org/10.1007/s12031-020-01658-w
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