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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impedes patients’ cognition, social, speech and communication skills. ASD is highly heterogeneous with a variety of etiologies and clinical manifestations. The prevalence rate of ASD increased steadily in recent years. Presently, molecular mechanisms underlying ASD occurrence and development remain to be elucidated. Here, we integrated multi-layer genomics data to investigate the transcriptome and pathway dysregulations in ASD development. The RNA sequencing (RNA-seq) expression profiles of induced pluripotent stem cells (iPSCs), neural progenitor cells (NPCs) and neuron cells from ASD and normal samples were compared in our study. We found that substantially more genes were differentially expressed in the NPCs than the iPSCs. Consistently, gene set variation analysis revealed that the activity of the known ASD pathways in NPCs and neural cells were significantly different from the iPSCs, suggesting that ASD occurred at the early stage of neural system development. We further constructed comprehensive brain- and neural-specific regulatory networks by incorporating transcription factor (TF) and gene interactions with long 5 non-coding RNA(lncRNA) and protein interactions. We then overlaid the transcriptomes of different cell types on the regulatory networks to infer the regulatory cascades. The variations of the regulatory cascades between ASD and normal samples uncovered a set of novel disease-associated genes and gene interactions, particularly highlighting the functional roles of ELF3 and the interaction between STAT1 and lncRNA ELF3-AS 1 in the disease development. These new findings extend our understanding of ASD and offer putative new therapeutic targets for further studies.