Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional analysis of human cardiac enhancers by tiling mutagenesis

ABSTRACT: Functional analysis of human cardiac enhancers by tiling mutagenesis

PROVIDER: PRJNA859125 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR20259106.fastq.gz	Fastqsanger.gz
	SRR20259107.fastq.gz	Fastqsanger.gz
	SRR20259108.fastq.gz	Fastqsanger.gz
	SRR20259109.fastq.gz	Fastqsanger.gz
	SRR20259110.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Functional analysis of human cardiac enhancers by tiling mutagenesis

Project description:To further determine the sequence features of active cardiac enhancers, 123 cardiac enhancers were functionally dissected by 10 bp tiling deletion-based mutagenesis MPRA in iPSC-CMs.

2023-11-16 | GSE208284 | GEO

Functional dissection of human cardiac enhancers and non-coding de novo variants in congenital heart disease

Project description:About 45% of congenital heart disease (CHD) is caused by rare gene mutations. Non-coding mutations that perturb cis-regulatory elements (CREs) likely contribute to CHD among the remaining cases without clear etiology. However, identifying CHD-causing non-coding variants has been problematic. We combined human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) differentiation and a lentivirus-mediated massively parallel reporter assay (lentiMPRA) to create a high-throughput platform to measure human cardiac enhancer activity. We tested 2451 candidate human cardiac enhancers, identified 1185 with measurable activity, and functionally dissected 123 of these by systematic tiling mutagenesis. We functionally evaluated 6761 non-coding de novo variants (ncDNVs) prioritized from the whole genome sequencing (WGS) of 749 CHD trios. 397 ncDNVs significantly affected cardiac CRE activity. Remarkably, 53% of these ncDNVs increased enhancer activity, often at regions with undetectable enhancer activity in the reference sequence. We introduced 10 of these DNVs associated with CHD genes into iPSCs and found that 4 altered expression of neighboring genes. Moreover, these 4 DNVs also altered cardiomyocyte differentiation, as assessed by single nucleus RNA sequencing. Using the MPRA data, we developed a regression model to prioritize future DNVs for functional testing and demonstrate that this model finds enrichment of DNVs in a second, independent WGS cohort. Taken together, we developed a scalable system to measure the impact of non-coding DNVs on CRE activity and deployed this platform to systematically assess the contribution of non-coding DNVs to CHD.

2022-08-05 | GSE210376 | GEO

Functional dissection of human cardiac enhancers with hiPSC-CMs and lentiMPRA

Project description:Functional dissection of human cardiac enhancers with hiPSC-CMs and lentiMPRA

| PRJNA870221 | ENA

Genome-wide landscape and functional necessity of heart enhancers

Project description:Analysis of the transcriptional changes in the heart resulting from the loss of cardiac enhancers. As there remains a limited understanding of the phenotypic consequences of enhancer mutations, we examined the impact of loss of function mutations by deleting two enhancers near heart disease genes in mice. In both cases, we observed loss of target gene expression, as well as cardiac phenotypes consistent with heart disease in humans, highlighting the functional importance of enhancers for normal heart function, as well as the potential contribution of enhancer mutations to heart disease. Hearts were dissected from wild-type and enhancer-null mice (either embryonic or adult) and processed for deep RNA-seq analysis.

2016-09-06 | E-GEOD-75907 | biostudies-arrayexpress

Functional dissection of human cardiac enhancers with hiPSC-CMs and lentiMPRA

Project description:To assess human cardiac enhancer activity, 400 bp candidate cardiac enhancers and controls were tested in iPSC-CMs using lentiMPRA.

2023-11-16 | GSE211417 | GEO

Pittsburgh Functional Cardiac Genomic Project

Project description:Pittsburgh Functional Cardiac Genomic Project

| PRJNA671399 | ENA

Genome-wide landscape and functional necessity of heart enhancers

2016-09-06 | GSE75907 | GEO

Functional enhancers shape extrachromosomal oncogene amplifications

Project description:Functional enhancers shape extrachromosomal oncogene amplifications

| PRJNA579579 | ENA

Extensive Functional Redundancy of Mammalian Enhancers

Project description:Extensive Functional Redundancy of Mammalian Enhancers

| PRJNA362215 | ENA

Functional dissection of human mitotic proteins using CRISPR-Cas9 tiling screens

Project description:Kinetochores are large protein assemblies that mark the centromere and bind to mitotic spindle microtubules to ensure accurate chromosome segregation. Like most protein-coding genes, the full multifunctional nature of kinetochore factors remains uncharacterized due to the limited experimental tools for unbiased dissection of human protein sequences. Here, we develop a method that leverages CRISPR-Cas9 induced mutations to comprehensively identify key functional regions within protein sequences that are required for cellular outgrowth. Our analysis of 48 human kinetochore genes revealed hundreds of regions required for cell proliferation, corresponding to known and uncharacterized protein domains. We biologically validated 15 of these regions, including amino acids 387-402 of Mad1, which when deleted compromise Mad1 kinetochore localization and chromosome segregation fidelity. Altogether, we demonstrate that CRISPR-Cas9-based tiling mutagenesis enables de novo identification of key functional domains in protein-coding genes, which elucidates separation of function mutants and allows functional annotation across the human proteome

2023-01-26 | GSE179188 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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