Molecular changes in specific types of neural cells and brain circuits correlate with the clinical severity of autism spectrum disorder, a new single-cell analysis of brain cells from autism patients finds. The results highlight what the authors refer to as autism-specific genes, or genes that represent high-priority targets for new therapeutic treatments for the disorder, though future studies involving larger patient cohorts are needed. Autism spectrum disorder (ASD), a developmental disorder encompassing a range of conditions and severities, affects 1 in 59 children in the U.S. and can impart social, communication and behavioral challenges. The genetic expression profile related to the disorder has been shown to widely vary. While hundreds of ASD susceptibility genes have been identified, none have been found to account for more than a small subset of cases. Despite the spectrum of clinical and genetic manifestations of autism, however, bulk gene expression studies have shown that the disorder affects cellular pathways and common genes. While related brain changes have been observed across autism patients, the specific cell types involved are unknown and have only recently become feasible to study. Dmitry Velmeshev and colleagues performed unbiased single-nuclease RNA sequencing to analyze the transcriptomes of single brain cells, including neurons and glia, from the brain tissue of patients affected with ASD. Studies in patients with epilepsy, often a co-morbidity of ASD, and in healthy people, helped confirm the genetic changes most closely associated with autism. Among the more than 100,000 single-nuclei gene expression profiles generated by the analysis, Velmeshev et al. discovered the pathways most affected by ASD were those that regulate synapse function as well as neuronal migration and outgrowth. What's more, the authors discovered that dysregulation of specific sets of genes expressed in upper-layer projection neurons correlate with the behavioral manifestations of ASD. Velmeshev et al. provide their dataset describing transcriptomic and ASD-associated gene expression changes across neuronal and glial cell types in an interactive web browser: https://cells.ucsc.edu/dev/?ds=autism.