Identification of Bacterial Lipopolysaccharide-Associated Genes and Molecular Subtypes in Autism Spectrum Disorder.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics & Personalized Medicine Pub Date : 2025-01-17 eCollection Date: 2025-01-01 DOI:10.2147/PGPM.S494126

Yuanxia He, Yun He, Boli Cheng

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引用次数: 0

Abstract

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by diverse symptoms affecting social interaction, communication, and behavior. This research aims to explore bacterial lipopolysaccharide (LPS)- and immune-related (BLI) molecular subgroups in ASD to enhance understanding of the disorder.

Methods: We analyzed 89 control samples and 157 ASD samples from the GEO database, identifying BLI signatures using least absolute shrinkage and selection operator regression (LASSO) and logistic regression machine learning algorithms. A nomogram prediction model was developed based on these signatures, and we performed Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and immune cell infiltration analysis to assess the impact of BLI subtypes and their underlying mechanisms.

Results: Our findings revealed 17 differentially expressed BLI genes in children with ASD, with BLNK, MAPK8, PRKCQ, and TNFSF12 identified as potential biomarkers. The nomogram demonstrated high diagnostic accuracy for ASD. We delineated two distinct molecular subtypes (Cluster 1 and Cluster 2), with GSVA indicating that Cluster 2 showed upregulation of immune- and inflammation-related pathways. This cluster exhibited increased levels of antimicrobial agents, chemokines, cytokines, and TNF family cytokines, alongside activation of bacterial lipoprotein-related pathways. A significant correlation was found between these pathways and distinct immune cell subtypes, suggesting a potential mechanism for neuroinflammation and immune cell infiltration in ASD.

Conclusion: Our research highlights the role of BLI-associated genes in the immune responses of individuals with ASD, indicating their contribution to the disorder's typification. The interplay between bacterial components, genetic predisposition, and immune dysregulation offers new insights for understanding ASD and developing personalized interventions.

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自闭症谱系障碍细菌脂多糖相关基因和分子亚型的鉴定。

背景：自闭症谱系障碍（ASD）是一种复杂的神经发育疾病，以影响社会互动、沟通和行为的多种症状为特征。本研究旨在探讨细菌脂多糖（LPS）和免疫相关（BLI）分子亚群在ASD中的作用，以提高对该疾病的认识。方法：对GEO数据库中的89个对照样本和157个ASD样本进行分析，采用最小绝对收缩、选择算子回归（LASSO）和逻辑回归机器学习算法识别BLI特征。基于这些特征，我们建立了一个nomogram预测模型，并进行了基因集富集分析（GSEA）、基因集变异分析（GSVA）和免疫细胞浸润分析，以评估BLI亚型的影响及其潜在机制。结果：我们的研究结果揭示了17个在ASD儿童中差异表达的BLI基因，其中BLNK、MAPK8、PRKCQ和TNFSF12被确定为潜在的生物标志物。该图对ASD具有较高的诊断准确性。我们描述了两种不同的分子亚型（集群1和集群2），GSVA表明集群2显示免疫和炎症相关途径的上调。该簇表现出抗菌药物、趋化因子、细胞因子和TNF家族细胞因子水平的增加，同时细菌脂蛋白相关途径的激活。这些通路与不同的免疫细胞亚型之间存在显著相关性，提示ASD中神经炎症和免疫细胞浸润的潜在机制。结论：我们的研究强调了bli相关基因在ASD个体免疫反应中的作用，表明它们对该疾病的分型有贡献。细菌成分、遗传易感性和免疫失调之间的相互作用为理解ASD和制定个性化干预措施提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

3.30

自引率

5.30%

发文量

110

审稿时长

16 weeks

期刊介绍： Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.