Jacokes Zachary, Adoremos Ian, Hussain Arham Rameez, Newman Benjamin T, Pelphrey Kevin A, Van Horn John Darrell
School of Data Science, University of Virginia, Charlottesville, VA 22903, United States of America.
College of Computer, Mathematical, and Natural Sciences, University of Maryland, Charlottesville, VA 22903, United States of America.
Pac Symp Biocomput. 2025;30:614-630. doi: 10.1142/9789819807024_0044.
Autism Spectrum Disorder (ASD) encompasses a range of developmental disabilities marked by differences in social functioning, cognition, and behavior. Both genetic and environmental factors are known to contribute to ASD, yet the exact etiological factors remain unclear. Developing integrative models to explore the effects of gene expression on behavioral and cognitive traits attributed to ASD can uncover environmental and genetic interactions. A notable aspect of ASD research is the sex-wise diagnostic disparity: males are diagnosed more frequently than females, which suggests potential sex-specific biological influences. Investigating neuronal microstructure, particularly axonal conduction velocity offers insights into the neural basis of ASD. Developing robust models that evaluate the vast multidimensional datasets generated from genetic and microstructural processing poses significant challenges. Traditional feature selection techniques have limitations; thus, this research aims to integrate principal component analysis (PCA) with supervised machine learning algorithms to navigate the complex data space. By leveraging various neuroimaging techniques and transcriptomics data analysis methods, this methodology builds on traditional implementations of PCA to better contextualize the complex genetic and phenotypic heterogeneity linked to sex differences in ASD and pave the way for tailored interventions.
自闭症谱系障碍(ASD)涵盖一系列发育障碍,其特征是社交功能、认知和行为存在差异。已知遗传和环境因素都会导致ASD,但确切的病因仍不清楚。开发综合模型以探索基因表达对ASD所致行为和认知特征的影响,可以揭示环境与基因的相互作用。ASD研究的一个显著方面是性别诊断差异:男性被诊断出ASD的频率高于女性,这表明可能存在特定性别的生物学影响。研究神经元微观结构,特别是轴突传导速度,有助于深入了解ASD的神经基础。开发强大的模型来评估从基因和微观结构处理中生成的大量多维数据集面临重大挑战。传统的特征选择技术存在局限性;因此,本研究旨在将主成分分析(PCA)与监督机器学习算法相结合,以在复杂的数据空间中导航。通过利用各种神经成像技术和转录组学数据分析方法,该方法基于PCA的传统实现方式,更好地将与ASD性别差异相关的复杂遗传和表型异质性置于具体情境中,并为量身定制的干预措施铺平道路。