Exploring preservation of autism spectrum disorder dysregulated co-expression modules in accessible cell models

Introduction: Autism spectrum disorder (ASD) affects more than 1 % of the population, and there is no biomarker to diagnose this condition. Dysregulation of co-expressed gene modules has been observed in neuronal cells of ASD individuals, suggesting that the expression profile of these genes could be used as a biomarker for the disorder. Brain tissue biopsy is impractical, and neuron acquisition through cell reprogramming is resource-intensive. Objectives: Identify accessible cell models reflecting co-expression modules that are dysregulated in ASD neuronal cells. Methods: Three groups of neuronal modules previously implicated in ASD (synapse, immune response, and translation modules) were assessed for preservation in transcriptomes from peripheral blood, urine-derived epithelial cells (UEC), umbilical cord blood (UCB) and dermal papilla stem cells (DPSC), using WGCNA (weighted gene co-expression analysis). Results: Thirteen studies (blood [5], UEC [2], DPSC [2], UCB [4]) were analyzed. The ASD-associated modules related to translation and immune response have showed a consistent moderate preservation in UEC and blood transcriptome studies. Despite moderate preservation, validation analysis using ASD blood transcriptome data revealed no significant differences between ASD individuals and controls. This result may be explained by the lack of preservation in selected studies, potentially influenced by technical factors. Our findings suggest that further validation is necessary, particularly focusing on protocol consistency and data processing, as accessible tissues like UEC and blood may offer a promising direction for developing non-invasive biomarkers for ASD.