Single-cell genomics and regulatory networks for 388 human brains [preprint]

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, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Source

Emani PS, Liu JJ, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee CY, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X; PsychENCODE Consortium; Bakken TE, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard JF, Gancz M, Garrido-Martín D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman GE, Huang A, Jiang Y, Jin T, Jorstad NL, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran JR, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan AS, Riesenmy TR, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini KJ, Wamsley B, Wang G, Xia Y, Xiao S, Yang AC, Zheng S, Gandal MJ, Lee D, Lein ES, Roussos P, Sestan N, Weng Z, White KP, Won H, Girgenti MJ, Zhang J, Wang D, Geschwind D, Gerstein M. Single-cell genomics and regulatory networks for 388 human brains. bioRxiv [Preprint]. 2024 Mar 30:2024.03.18.585576. doi: 10.1101/2024.03.18.585576. PMID: 38562822; PMCID: PMC10983939.

DOI

10.1101/2024.03.18.585576

Permanent Link to this Item

https://hdl.handle.net/20.500.14038/53375

PubMed ID

38562822

Notes

This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

Related Resources

Now published in Science doi: 10.1126/science.adi5199

Rights

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.; Attribution-NonCommercial-NoDerivatives 4.0 International

Distribution License

http://creativecommons.org/licenses/by-nc-nd/4.0/