Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [scATAC-seq]

ABSTRACT: Here we present Perturb-ATAC, a method which combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells, based on the simultaneous detection of CRISPR guide RNAs and open chromatin sites by Assay of Transposase-accessible Chromatin with sequencing (ATAC-seq). We applied Perturb-ATAC to transcription factors (TFs), chromatin-modifying factors, and noncoding RNAs (ncRNAs) in ~3,700 single cells, encompassing more than 75 unique genotype-phenotype relationships.

ORGANISM(S): Homo sapiens

PROVIDER: GSE116248 | GEO | 2018/12/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [Perturb-ATAC (ATAC)]

Project description:Here we present Perturb-ATAC, a method which combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells, based on the simultaneous detection of CRISPR guide RNAs and open chromatin sites by Assay of Transposase-accessible Chromatin with sequencing (ATAC-seq). We applied Perturb-ATAC to transcription factors (TFs), chromatin-modifying factors, and noncoding RNAs (ncRNAs) in ~3,700 single cells, encompassing more than 75 unique genotype-phenotype relationships.

2018-12-20 | GSE116249 | GEO

Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [Bulk ATAC-seq]

2018-12-20 | GSE116247 | GEO

Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [Perturb-ATAC (GBC/sgRNA)]

2018-12-20 | GSE116285 | GEO

Scalable pooled CRISPR screens with single cell chromatin accessibility profiling.

Project description:A scalable, cost-effective method that combines CRISPR perturbations with a single-cell indexing assay for transposase-accessible chromatin (CRISPR-sciATAC). This method links genome-wide chromatin accessibility to genetic perturbations through simultaneous capture of ATAC-seq fragments and CRISPR guide RNAs from single cells using a 96-well plate combinatorial indexing approach.

2020-11-07 | GSE161002 | GEO

Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [Perturb-ATAC (ATAC)]

Project description:Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [Perturb-ATAC (ATAC)]

| PRJNA478045 | ENA

A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response

Project description:Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. A genome-scale CRISPR interference (CRISPRi) screen identified genes whose depletion perturbs ER homeostasis. Subjecting ~100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses revealed epistasis among the three UPR branches, bifurcated UPR branch activation between cells subject to the same perturbation, and differential activation of the branches across hits, including a feedback loop between the translocon and the IRE1α branch. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses.

2016-12-15 | GSE90546 | GEO

Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [Perturb-ATAC (GBC/sgRNA)]

Project description:Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [Perturb-ATAC (GBC/sgRNA)]

| PRJNA478048 | ENA

Perturb-map coupled with spatial transcriptomics identifies mutation associated gene signatures in a mouse model of lung adenocarcinoma

Project description:The cellular architecture of a tumor has a major impact on cancer outcome, and thus there is interest in identifying genes controlling the tumor microenvironment (TME). While CRISPR screens are helping uncover genes regulating many cell-intrinsic processes, existing approaches are suboptimal for identifying gene functions operating extracellularly or within a tissue context. To address this, we developed an approach for spatial functional genomics called Perturb-map, which utilizes protein barcodes (Pro-Code) to enable spatial detection of barcoded cells within tissue. We applied Perturb-map to knockout dozens of genes in parallel in a mouse model of lung cancer and simultaneously assessed how each knockout influenced tumor growth, histopathology, and immune composition. Additionally, we paired Perturb-map and spatial transcriptomics for unbiased molecular analysis of Pro-Code/CRISPR lesions. Our studies found in Tgfbr2 knockout lesions, the TME was converted to a fibro-mucinous state and T-cells excluded, concomitant with upregulated TGFb and TGFb-mediated stroma activation, suggesting Tgfbr2 loss on lung cancer cells increased TGFb bioavailability and enhanced its suppressive effects on the TME. These studies establish Perturb-map for functional genomics within a tissue at single cell-resolution with spatial architecture preserved.

2022-01-15 | GSE193460 | GEO

Single-cell chromatin accessibility data using scATAC-seq

Project description:A single hematopoietic stem cell can give rise to all blood cells with remarkable fidelity. Here, we define the chromatin accessibility and transcriptional landscape controlling this process in thirteen primary cell types that traverse the hematopoietic hierarchy. Exploiting the finding that enhancer landscapes better reflect cell identity than mRNA levels, we enable "enhancer cytometry" for accurate enumeration of pure cell types from complex populations. We further reveal the lineage ontogeny of genetic elements linked to diverse human diseases. In acute myeloid leukemia, chromatin accessibility reveals distinctive regulatory evolution in pre-leukemic HSCs (pHSCs), leukemia stem cells, and leukemic blasts. These leukemic cells demonstrate unique lineage infidelity, confirmed by single cell regulomes. We further show that pHSCs have a competitive advantage that is conferred by reduced chromatin accessibility at HOXA9 targets and is associated with adverse patient outcomes. Thus, regulome dynamics can provide diverse insights into human hematopoietic development and disease. Single-cell ATAC-seq of LMPPs, Monocytes, LSCs and Luekemic blast cells.

2016-06-01 | E-GEOD-74310 | biostudies-arrayexpress

Single-cell chromatin accessibility data using scATAC-seq

Project description:Cell-to-cell variation is a universal feature of life that impacts a wide range of biological phenomena, from developmental plasticity to tumor heterogeneity. While recent advances have improved our ability to document cellular phenotypic variation the fundamental mechanisms that generate variability from identical DNA sequences remain elusive. Here we reveal the landscape and principles of cellular DNA regulatory variation by developing a robust method for mapping the accessible genome of individual cells via assay of transposase accessible chromatin sequencing (ATAC-seq). Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single-cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provides insights into cell-to-cell variation. Accessibility variance is systematically associated with specific trans-factors and cis-elements, and we discover combinations of trans-factors associated with either induction or suppression of cell-to-cell variability. We further identify sets of trans-factors associated with cell-type specific accessibility variance across 6 cell types. Targeted perturbations of cell cycle or transcription factor signaling evoke stimulus-specific changes in this observed variability. The pattern of accessibility variation in cis across the genome recapitulates chromosome topological domains de novo, linking single-cell accessibility variation to three-dimensional genome organization. All together, single-cell analysis of DNA accessibility provides new insight into cellular variation of the “regulome.” Profiles of single cell epigenomes, assayed using scATAC-seq, across 8 cell types and 4 targeted cell manipulations. The complete data set contains a total of 1,632 assayed wells.

2015-06-17 | E-GEOD-65360 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data