Autism spectrum disorder (ASD) is a common neurodevelopmental condition, yet early diagnosis remains difficult because it relies on behavioral features that often emerge only after infancy. The absence of clinically validated biomarkers limits the identification of ASD during the early developmental window when interventions are most effective. Although ASD affects the brain, access to neural tissue is extremely limited, and postmortem studies, while informative, are constrained by small sample sizes and potential confounders. Genomic studies have identified high-confidence ASD risk genes, many encoding regulators of transcription and RNA processing, and analyses of ASD postmortem cortex reveal widespread disruption of alternative splicing, suggesting that splicing dysregulation is a convergent molecular mechanism in ASD. This collaborative project combines the Salton lab’s expertise in RNA splicing with the Shifman lab’s expertise in genetics and bioinformatics and their shared interest in ASD. We will systematically characterize ASD-associated splicing alterations in lymphoblastoid cell lines from thousands of ASD probands and unaffected siblings. By integrating differential splicing analysis, regulatory motif and chromatin feature enrichment, comparison with ASD brain signatures, and individual-level “splicing burden” scores, we aim to define the regulatory and biological relevance of peripheral splicing changes and evaluate their potential as biomarkers.