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Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD

Post-traumatic stress disorder (PTSD) is a polygenic disorder occurring after extreme trauma exposure. Recent studies have begun to detail the molecular biology of PTSD. However, given the array of PTSD-perturbed molecular pathways identifed so far, …

Impeller: a path-based heterogeneous graph learning method for spatial transcriptomic data imputation

Recent advances in spatial transcriptomics allow spatially resolved gene expression measurements with cellular or even sub-cellular resolution, directly characterizing the complex spatiotemporal gene expression landscape and cell-to-cell interactions …

A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex

The molecular organization of the human neocortex historically has been studied in the context of its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification of transcriptionally defined spatial …

Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain

Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is …

Massively parallel characterization of regulatory elements in the developing human cortex

Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the …

Single-cell genomics and regulatory networks for 388 human brains

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics …

Single-cell multi-cohort dissection of the schizophrenia transcriptome

The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation and the development of more effective therapies. Here, we performed single-cell dissection of schizophrenia-associated transcriptomic changes in the human …

Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data

Sample-wise deconvolution methods estimate cell-type proportions and gene expressions in bulk tissue samples, yet their performance and biological applications remain unexplored, particularly in human brain transcriptomic data. Here, nine …

Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders

Many psychiatric disorders exhibit sex differences, but the underlying mechanisms remain poorly understood. We analyzed transcriptomics data from 2160 postmortem adult prefrontal cortex brain samples from the PsychENCODE consortium in a …

Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements

Most genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from the PsychENCODE Consortium and other published sources to …