Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements DOI Open Access
Florence M. Chardon, Troy A. McDiarmid, Nicholas F. Page

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 28, 2023

CRISPR-based gene activation (CRISPRa) is a promising therapeutic approach for therapy, upregulating expression by targeting promoters or enhancers in tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive

Language: Английский

Systematic differences in discovery of genetic effects on gene expression and complex traits DOI
Hakhamanesh Mostafavi, Jeffrey P. Spence,

Sahin Naqvi

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(11), P. 1866 - 1875

Published: Oct. 19, 2023

Language: Английский

Citations

157
CRISPR technologies for genome, epigenome and transcriptome editing DOI
Lukas Villiger,

Julia Joung,

Luke W. Koblan

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 464 - 487

Published: Feb. 2, 2024

Language: Английский

Citations

73
Convergence of coronary artery disease genes onto endothelial cell programs DOI

Gavin R. Schnitzler,

Helen Y. Kang,

Shi Fang

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(8000), P. 799 - 807

Published: Feb. 7, 2024

Language: Английский

Citations

34
Pleiotropy, epistasis and the genetic architecture of quantitative traits DOI
Trudy F. C. Mackay, Robert R. H. Anholt

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: 25(9), P. 639 - 657

Published: April 2, 2024

Language: Английский

Citations

28
Tissue-specific enhancer–gene maps from multimodal single-cell data identify causal disease alleles DOI
Saori Sakaue, Kathryn Weinand, Shakson Isaac

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(4), P. 615 - 626

Published: April 1, 2024

Language: Английский

Citations

23
Deciphering the impact of genomic variation on function DOI
J Engreitz, Heather A. Lawson, Harinder Singh

et al.

Nature, Journal Year: 2024, Volume and Issue: 633(8028), P. 47 - 57

Published: Sept. 4, 2024

Language: Английский

Citations

22
Genetic and molecular architecture of complex traits DOI Creative Commons
Tuuli Lappalainen, Yang Li, Sohini Ramachandran

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(5), P. 1059 - 1075

Published: Feb. 1, 2024

Language: Английский

Citations

21
Systematic reconstruction of molecular pathway signatures using scalable single-cell perturbation screens DOI
Longda Jiang, Carol Dalgarno, Efthymia Papalexi

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

Citations

2
Scalable genetic screening for regulatory circuits using compressed Perturb-seq DOI Creative Commons
Douglas Yao, Loïc Binan, Jon Bezney

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(8), P. 1282 - 1295

Published: Oct. 23, 2023

Abstract Pooled CRISPR screens with single-cell RNA sequencing readout (Perturb-seq) have emerged as a key technique in functional genomics, but they are limited scale by cost and combinatorial complexity. In this study, we modified the design of Perturb-seq incorporating algorithms applied to random, low-dimensional observations. Compressed measures multiple random perturbations per cell or cells droplet computationally decompresses these measurements leveraging sparse structure regulatory circuits. Applied 598 genes immune response bacterial lipopolysaccharide, compressed achieves same accuracy conventional an order magnitude reduction greater power learn genetic interactions. We identified known novel regulators responses uncovered evolutionarily constrained downstream targets enriched for disease heritability, including many missed existing genome-wide association studies. Our framework enables new scales interrogation foundational method genomics.

Language: Английский

Citations

38
Characterizing the Shared Genetic Underpinnings of Schizophrenia and Cardiovascular Disease Risk Factors DOI
Linn Rødevand, Zillur Rahman, Guy Hindley

et al.

American Journal of Psychiatry, Journal Year: 2023, Volume and Issue: 180(11), P. 815 - 826

Published: Sept. 27, 2023

Schizophrenia is associated with increased risk of cardiovascular disease (CVD), although there variation in among individuals. There are indications shared genetic etiology between schizophrenia and CVD, but the nature overlap remains unclear. The aim this study was to fill gap knowledge.Overlapping architectures CVD factors were assessed by analyzing recent genome-wide association (GWAS) results. bivariate causal mixture model (MiXeR) applied estimate number variants conjunctional false discovery rate (conjFDR) approach used pinpoint specific loci.Extensive found factors, particularly smoking initiation (N=8.6K variants) body mass index (BMI) (N=8.1K variants). Several loci detected BMI (N=304), waist-to-hip ratio (N=193), (N=293), systolic (N=294) diastolic (N=259) blood pressure, type 2 diabetes (N=147), lipids (N=471), coronary artery (N=35). had mainly concordant effect directions, opposite directions. overlapping lipids, ratio, diabetes, mixed Functional analyses implicated mapped genes that expressed brain tissue immune cells.These findings indicate a propensity reduced obesity individuals schizophrenia. bidirectional effects other may imply differences liability across subgroups, possibly underlying comorbidity.

Language: Английский

Citations

36