Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum Disorder
Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with clinical presentation and prognostic heterogeneity. Ferroptosis is a regulated non-apoptotic cell death program implicated in the occurrence and progression of various diseases. Therefore, we aimed to explore ferropto...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.911119/full |
| _version_ | 1811217285251072000 |
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| author | Lichun Liu Yongxing Lai Zhidong Zhan Qingxian Fu Yuelian Jiang |
| author_facet | Lichun Liu Yongxing Lai Zhidong Zhan Qingxian Fu Yuelian Jiang |
| author_sort | Lichun Liu |
| collection | DOAJ |
| description | Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with clinical presentation and prognostic heterogeneity. Ferroptosis is a regulated non-apoptotic cell death program implicated in the occurrence and progression of various diseases. Therefore, we aimed to explore ferroptosis-related molecular subtypes in ASD and further illustrate the potential mechanism.Methods: A total of 201 normal samples and 293 ASD samples were obtained from the Gene Expression Omnibus (GEO) database. We used the unsupervised clustering analysis to identify the molecular subtypes based on ferroptosis-related genes (FRGs) and evaluate the immune characteristics between ferroptosis subtypes. Ferroptosis signatures were identified using the least absolute shrinkage and selection operator regression (LASSO) and recursive feature elimination for support vector machines (SVM-RFE) machine learning algorithms. The ferroptosis scores based on seven selected genes were constructed to evaluate the ferroptosis characteristics of ASD.Results: We identified 16 differentially expressed FRGs in ASD children compared with controls. Two distinct molecular clusters associated with ferroptosis were identified in ASD. Analysis of immune infiltration revealed immune heterogeneity between the two clusters. Cluster2, characterized by a higher immune score and a larger number of infiltrated immune cells, exhibited a stronger immune response and was markedly enriched in immune response-related signaling pathways. Additionally, the ferroptosis scores model was capable of predicting ASD subtypes and immunity. Higher levels of ferroptosis scores were associated with immune activation, as seen in Cluster2. Lower ferroptosis scores were accompanied by relative immune downregulation, as seen in Cluster1.Conclusion: Our study systematically elucidated the intricate correlation between ferroptosis and ASD and provided a promising ferroptosis score model to predict the molecular clusters and immune infiltration cell profiles of children with ASD. |
| first_indexed | 2024-04-12T06:51:37Z |
| format | Article |
| id | doaj.art-8edcfc991069492d8f9a2cb9e9d87fb3 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T06:51:37Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-8edcfc991069492d8f9a2cb9e9d87fb32022-12-22T03:43:17ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.911119911119Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum DisorderLichun Liu0Yongxing Lai1Zhidong Zhan2Qingxian Fu3Yuelian Jiang4Department of Pharmacy, Fujian Children’s Hospital, Fuzhou, ChinaDepartment of Geriatric Medicine, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, ChinaDepartment of Pediatric Intensive Care Unit, Fujian Children’s Hospital, Fuzhou, ChinaDepartment of Pediatric Endocrinology, Fujian Children’s Hospital, Fuzhou, ChinaDepartment of Pharmacy, Fujian Children’s Hospital, Fuzhou, ChinaIntroduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with clinical presentation and prognostic heterogeneity. Ferroptosis is a regulated non-apoptotic cell death program implicated in the occurrence and progression of various diseases. Therefore, we aimed to explore ferroptosis-related molecular subtypes in ASD and further illustrate the potential mechanism.Methods: A total of 201 normal samples and 293 ASD samples were obtained from the Gene Expression Omnibus (GEO) database. We used the unsupervised clustering analysis to identify the molecular subtypes based on ferroptosis-related genes (FRGs) and evaluate the immune characteristics between ferroptosis subtypes. Ferroptosis signatures were identified using the least absolute shrinkage and selection operator regression (LASSO) and recursive feature elimination for support vector machines (SVM-RFE) machine learning algorithms. The ferroptosis scores based on seven selected genes were constructed to evaluate the ferroptosis characteristics of ASD.Results: We identified 16 differentially expressed FRGs in ASD children compared with controls. Two distinct molecular clusters associated with ferroptosis were identified in ASD. Analysis of immune infiltration revealed immune heterogeneity between the two clusters. Cluster2, characterized by a higher immune score and a larger number of infiltrated immune cells, exhibited a stronger immune response and was markedly enriched in immune response-related signaling pathways. Additionally, the ferroptosis scores model was capable of predicting ASD subtypes and immunity. Higher levels of ferroptosis scores were associated with immune activation, as seen in Cluster2. Lower ferroptosis scores were accompanied by relative immune downregulation, as seen in Cluster1.Conclusion: Our study systematically elucidated the intricate correlation between ferroptosis and ASD and provided a promising ferroptosis score model to predict the molecular clusters and immune infiltration cell profiles of children with ASD.https://www.frontiersin.org/articles/10.3389/fgene.2022.911119/fullautism spectrum disorderferroptosismolecular clustersimmune characteristicspredictive model |
| spellingShingle | Lichun Liu Yongxing Lai Zhidong Zhan Qingxian Fu Yuelian Jiang Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum Disorder Frontiers in Genetics autism spectrum disorder ferroptosis molecular clusters immune characteristics predictive model |
| title | Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum Disorder |
| title_full | Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum Disorder |
| title_fullStr | Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum Disorder |
| title_full_unstemmed | Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum Disorder |
| title_short | Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum Disorder |
| title_sort | identification of ferroptosis related molecular clusters and immune characterization in autism spectrum disorder |
| topic | autism spectrum disorder ferroptosis molecular clusters immune characteristics predictive model |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.911119/full |
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