In a highly collaborative effort involving three laboratories, Daniel Geschwind, Michael Gandal and Dorothy Schafer plan to explore the relationship between cortical and thalamic changes in ASD postmortem brain samples using single-cell genomic approaches, including RNAseq, ATAC-seq and spatial transcriptomics by MERFISH. This will allow for a comprehensive evaluation of the molecular changes in these circuits and their relationship to each other at a cellular level.

In the current project, Basilis Zikopoulos and Arash Yazdanbakhsh plan to use sophisticated methodologies of machine learning to classify white matter cortical pathways in postmortem brain tissue samples from individuals with ASD and neurotypical individuals. Results from this study will provide novel data on key features of typical cortical white matter pathways and axon pathology in ASD.

White matter tracts are brain regions that have been understudied at the cellular and molecular level yet are clearly functionally altered in individuals with ASD. In the current project, Genevieve Konopka plans to assess the molecular make-up of the cellular constituents of white matter tracts in postmortem brain tissue from individuals with ASD compared with neurotypical individuals.

In this study, Christopher Walsh and Peter Park aim to better understand the pathogenesis of ASD through the characterization and functional analysis of somatic mutations identified by direct sequencing of DNA derived from postmortem brain tissues of individuals who were diagnosed with ASD.