Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced bioinformatics and explainable AI to analyze gene expression associated with ASD, using data from five GEO datasets. Among 351 neurotypical controls and 358 individuals with autism, we identified 3,339 Differentially Expressed Genes (DEGs) with an adjusted p-value (≤ 0.05). A subsequent meta-analysis pinpointed 342 DEGs (adjusted p-value ≤ 0.001), including 19 upregulated and 10 down-regulated genes across all datasets. Shared genes, pathogenic single nucleotide polymorphisms (SNPs), chromosomal positions, and their impact on biological pathways were examined. We identified potential biomarkers (HOXB3, NR2F2, MAPK8IP3, PIGT, SEMA4D, and SSH1) through text mining, meriting further investigation. Additionally, ‎we shed light on the roles of RPS4Y1 and KDM5D genes in neurogenesis and neurodevelopment. Our analysis detected 1,286 SNPs linked to ASD-related conditions, of which 14 high-risk SNPs were located on chromosomes 10 and X. We highlighted potential missense SNPs associated with FGFR inhibitors, suggesting that it may serve as a promising biomarker for responsiveness to targeted therapies. Our explainable AI model identified the MID2 gene as a potential ASD biomarker. This research unveils vital genes and potential biomarkers, providing a foundation for novel gene discovery in complex diseases.

自闭症谱系障碍 (ASD) 是一种复杂的神经发育疾病，其特征是大脑连接和功能改变。在这项研究中，我们采用先进的生物信息学和可解释的人工智能，使用来自五个 GEO 数据集的数据来分析与 ASD 相关的基因表达。在 351 名神经正常对照组和 358 名自闭症患者中，我们鉴定了 3,339 个差异表达基因 (DEG)，其 p 值经过调整 (≤ 0.05)。随后的荟萃分析确定了所有数据集中的 342 个 DEG（调整后的 p 值 ≤ 0.001），其中包括 19 个上调基因和 10 个下调基因。检查了共享基因、致病性单核苷酸多态性 (SNP)、染色体位置及其对生物途径的影响。我们通过文本挖掘确定了潜在的生物标志物（HOXB3、NR2F2、MAPK8IP3、PIGT、SEMA4D和SSH1），值得进一步研究。此外，我们还阐明了RPS4Y1和KDM5D基因在神经发生和神经发育中的作用。我们的分析检测到 1,286 个与 ASD 相关病症相关的 SNP，其中 14 个高风险 SNP 位于 10 号和 X 号染色体上。我们强调了与FGFR抑制剂相关的潜在错义 SNP，表明它可能作为靶向药物反应性的有前景的生物标志物。疗法。我们的可解释 AI 模型将MID2基因识别为潜在的 ASD 生物标志物。这项研究揭示了重要的基因和潜在的生物标志物，为复杂疾病中新基因的发现奠定了基础。