Cited by Advances in optical pooled screening to map spatial complexity

Transcriptome-wide characterization of genetic perturbations DOI

Ajay Nadig, Joseph M. Replogle, Angela N. Pogson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 3, 2024

Abstract Single cell CRISPR screens such as Perturb-seq enable transcriptomic profiling of genetic perturbations at scale. However, the data produced by these are often noisy due to cost and technical constraints, limiting power detect true effects with conventional differential expression analyses. Here, we introduce TRanscriptome-wide Analysis Differential Expression (TRADE), a statistical framework which estimates transcriptome-wide distribution from gene-level measurements. Within TRADE, derive multiple novel, interpretable metrics, including “transcriptome-wide impact”, an estimator overall transcriptional effect perturbation is stable across sampling depths. We analyze new published large-scale datasets show that many not statistically significant, but detectable in aggregate TRADE. In genome-scale screen, find typical gene affects estimated 45 genes, whereas essential over 500 genes. An advantage our approach its ability compare contexts dosages despite differences power. use this identify cell-type dependent examples where responses only larger magnitude, also qualitatively different, function dosage. Lastly, expand analysis case/control comparison for neuropsychiatric conditions, finding correlations greater than diagnoses. TRADE lays analytic foundation systematic atlases, well experiments more broadly.

Language: Английский

Citations

Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome DOI

Eli Metzner, Kaden M. Southard, Thomas M. Norman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 27, 2024

SUMMARY Single-cell CRISPR screens link genetic perturbations to transcriptional states, but high-throughput methods connecting these induced changes their regulatory foundations are limited. Here we introduce Multiome Perturb-seq, extending single-cell simultaneously measure perturbation-induced in gene expression and chromatin accessibility. We apply Perturb-seq a CRISPRi screen of 13 remodelers human RPE-1 cells, achieving efficient assignment sgRNA identities single nuclei via an improved method for capturing barcode transcripts from nuclear RNA. organize accessibility measurements into coherent programs describing the integrated effects on cell state, finding that ARID1A SUZ12 knockdowns induce enriched developmental features. Pseudotime analysis connects expression, highlighting value multimodal profiling. Overall, our provides scalable simply implemented system dissect logic underpinning state.

Language: Английский

Citations

Saturation profiling of drug-resistant genetic variants using prime editing DOI

Younggwang Kim, Hyeong-Cheol Oh, Seung‐Ho Lee

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Language: Английский

Citations

Precision mutational scanning: your multipass to the future of genetics DOI

Jonathan Roth,

Francisco J. Sánchez‐Rivera

Nature Methods, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Language: Английский

Citations

NIS-Seq enables cell-type-agnostic optical perturbation screening DOI

Caroline I. Fandrey,

Marius Jentzsch,

Peter Konopka

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

Language: Английский

Citations

Advances in optical pooled screening to map spatial complexity DOI

Maurice Kahnwald,

Marius Mählen,

Koen C. Oost

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

Language: Английский

Citations