ARC-SV, a novel probabilistic method for detecting complex structural variations (cxSVs), revealed cxSVs as a major driver of human genetic diversity and implicated them in neuropsychiatric disorders through effects on neural genes, chromatin accessibility, and gene expression in brain regions and cell types.
Multi-omic profiling of matched brain and peripheral tissues offer rare opportunities to uncover extra-CNS drivers of Alzheimer’s pathobiology. Here, authors report an Alzheimer’s linked CD83(+) microglia subtype that is associated with immunoglobulin IgG4 production in the transverse colon.
We present a comprehensive catalog that captures variation in the human brain regulome, which illuminates the cell type–specific molecular mechanisms that underlie neuropsychiatric and neurodegenerative disorders. Our work highlights an approach to move from statistical associations from large-scale GWASs to functionally validated variants and molecular mechanisms of disease.
Our population-scale single-cell resource for the human brain can help facilitate precision-medicine approaches for neuropsychiatric disorders, especially by prioritizing follow-up genes and drug targets linked to cell types.
Our results provide a valuable resource to investigate the molecular pathophysiology of schizophrenia at single-cell resolution, offering insights into preferential dysregulation of specific neuronal populations and their potential role in mediating genetic risk. Together, they suggest convergence of etiological genetic risk factors, neuronal transcriptional dysregulation, and symptomatic manifestation in schizophrenia.
We demonstrated that DeepGAMI improves phenotype prediction and prioritizes phenotypic features and networks in multiple multimodal datasets in complex brains and brain diseases.
Our results describe the complex regulation of cell composition at critical stages in lineage determination and shed light on the impact of spatiotemporal alterations in gene expression on neuropsychiatric disease.
We present a new atlas of bulk proteomics and DNA methylation, as well as cell-type-specific RNA-seq and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) data for deeply characterized AD samples.