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Single-cell genomics and regulatory networks for 388 human brains

Single-cell genomics and regulatory networks for 388 human brains

March 19, 2024 | Prashant S. Emanit, Jason J. Liu†, Declan Clarke†, Matthew Jensen†, Jonathan Warrell†, Chirag Gupta†, Ran Meng†, Che Yu Lee†, Siwei Xu†, Cagatay Dursun†, Shaoke Lou†, Yuhang Chen, Zhiyuan Chu, Timur Galeev, Ahyeon Hwang, Yunyang Li, Pengyu Ni, Xiao Zhou, PsychENCODE Consortium, Trygve E. Bakken, Jaroslav Bendl, Lucy Bicks, Tanima Chatterjee, Lijun Cheng, Yuyan Cheng, Yi Dai, Ziheng Duan, Mary Flaherty, John F. Fullard, Michael Gancz, Diego Garrido-Martín, Sophie Gaynor-Gillett, Jennifer Grundman, Natalie Hawken, Ella Henry, Gabriel E. Hoffman, Ao Huang, Yunzhe Jiang, Ting Jin, Nikolas L. Jorstad, Riki Kawaguchi, Saniya Khullar, Jianyin Liu, Junhao Liu, Shuang Liu, Shaojie Ma, Michael Margolis, Samantha Mazariegos, Jill Moore, Jennifer R. Moran, Eric Nguyen, Nishigandha Phalke, Milos Pjanic, Henry Pratt, Diana Quintero, Ananya S. Rajagopalan, Tiemon R. Riesemny, Nicole Shedd, Manman Shi, Megan Spector, Rosemarie Terwilliger, Kyle J. Travaglini, Brie Wamsley, Gaoyuan Wang, Yan Xia, Shaohua Xiao, Andrew C. Yang, Suchen Zheng, Michael J. Gandal, Donghoon Lee, Ed S. Lein, Panos Roussos, Nenad Sestan, Zhiping Weng, Kevin P. White, Hyejung Won, Matthew J. Girgenti*, Jing Zhang*, Daifeng Wang*, Daniel Geschwind*, Mark Gerstein*
This study presents a comprehensive resource, brainSCOPE, which integrates single-cell genomics and multi-omics data from 388 individuals to investigate brain disorders. The resource includes >2.8 million nuclei from the prefrontal cortex, covering 28 distinct brain cell types. Key findings include the identification of over 550,000 cell-type-specific regulatory elements and 1.4 million single-cell expression-quantitative trait loci (eQTLs). These eQTLs were used to build cell-type regulatory and cell-to-cell communication networks, revealing cellular changes in aging and neuropsychiatric disorders. The study also developed an integrative model that accurately imputes single-cell expression and simulates gene perturbations, prioritizing disease-risk genes and drug targets with associated cell types. The model's predictions were validated through CRISPR experiments, demonstrating its potential for precision medicine. Overall, brainSCOPE provides a rich resource for understanding brain disorders at the single-cell level.This study presents a comprehensive resource, brainSCOPE, which integrates single-cell genomics and multi-omics data from 388 individuals to investigate brain disorders. The resource includes >2.8 million nuclei from the prefrontal cortex, covering 28 distinct brain cell types. Key findings include the identification of over 550,000 cell-type-specific regulatory elements and 1.4 million single-cell expression-quantitative trait loci (eQTLs). These eQTLs were used to build cell-type regulatory and cell-to-cell communication networks, revealing cellular changes in aging and neuropsychiatric disorders. The study also developed an integrative model that accurately imputes single-cell expression and simulates gene perturbations, prioritizing disease-risk genes and drug targets with associated cell types. The model's predictions were validated through CRISPR experiments, demonstrating its potential for precision medicine. Overall, brainSCOPE provides a rich resource for understanding brain disorders at the single-cell level.
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