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Published on: September 6, 2024
Development and Validation of a Novel Diagnostic Model for Childhood Autism Spectrum Disorder Based on
Xiaolu Wu1, Ran Li2, Qin Hong1
1Department of Child Health Care, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
Insights
A new diagnostic model using ferroptosis-related genes aids in the early and precise diagnosis of autism spectrum disorder (ASD) in children. This model shows promise for timely intervention and treatment strategies.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a significant genetic basis.
- Ferroptosis, a regulated form of cell death, is increasingly implicated in neurological disorders.
Purpose of the Study:
- To develop a diagnostic model for early and precise diagnosis of childhood ASD using ferroptosis-related genes (FRGs).
Main Methods:
- Identified differentially expressed genes (DEGs) related to ferroptosis in ASD patients compared to typically developing controls.
- Utilized random forest analysis to select key FRGs for model construction.
- Validated the diagnostic model across multiple independent datasets.
Main Results:
- Identified 27 DEGs and selected four key FRGs for the diagnostic model.
- The model achieved AUC values of 0.7002 (training) and up to 0.7444 (validation datasets).
- A regulatory network suggested roles for RORA, EAF1, NFYB, miR-4703-3p, and miR-6073 in ASD development. Piperaquine showed potential as an ASD therapeutic.
Conclusions:
- A novel diagnostic model based on FRGs can aid in the precision diagnosis of childhood ASD.
- The findings support the role of ferroptosis in ASD pathogenesis and suggest potential therapeutic targets.
Abstract:
Autism spectrum disorder (ASD) is a highly genetic heterogeneous neurodevelopmental disorder, which is usually considered a heritable and heterogeneous neurodevelopmental disorder and has caused a great burden to society and families. Emerging roles of ferroptosis have been observed in neurological disorders. This study aimed to construct a diagnostic model based on ferroptosis-related genes (FRGs) to contribute to the early and precise diagnosis of childhood ASD. In the candidate FRGs, we identified 27 differentially expressed genes (DEGs) between ASD patients and typically developing (TD) controls. Four key FRGs were identified using the random forest analysis for further analysis. Utilization of the four gene expression, we constructed a diagnostic model and the AUC value in the training dataset (GSE18123) is 0.7002. We deem that a patient with a score less than 0.9904 is likely to have ASD. Three validation datasets (GSE111176, GSE113834, and GSE28521) were collected and the AUC value is 0.7442, 0.7444, and 0.6474, respectively. A multi-factor regulatory network based on four FRGs indicated that RORA, EAF1, NFYB, miR-4703-3p, and miR-6073 may play a role in the development of ASD. In addition, we found piperaquine may have the potential to be a promising drug for the treatment of ASD. Overall, we constructed a diagnostic model of childhood ASD, which could contribute to the precision diagnosis and timely treatment of childhood ASD.
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