Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide CRISPR screen identifies cell cycle as a synthetic lethal pathway with SRSF2P95H mutation

ABSTRACT: Genome-wide CRISPR screen identifies cell cycle as a synthetic lethal pathway with SRSF2P95H mutation

PROVIDER: PRJNA694743 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR13527638_1.fastq.gz	Fastqsanger.gz
	SRR13527638_2.fastq.gz	Fastqsanger.gz
	SRR13527639_1.fastq.gz	Fastqsanger.gz
	SRR13527639_2.fastq.gz	Fastqsanger.gz
	SRR13527640_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 48

Similar Datasets

Genome-wide CRISPR screen identifies cell cycle as a synthetic lethal pathway with SRSF2P95H mutation

Project description:Current strategies to target RNA splicing mutant myeloid cancers propose disruption of normal splicing activity by targeting the splicing apparatus therapeutically. This approach is only modestly sensitizing and is also toxic to non-mutant bearing wild-type cells. To explore potentially exploitable genetic interactions with spliceosome mutations, we combined data mining and functional screening for synthetic lethal interactions with an Srsf2P95H/+ mutation. Analysis of mis-splicing events in a series of both human and murine SRSF2P95H mutant samples across multiple myeloid diseases (AML, MDS, CMML) was first performed to identify conserved mis-splicing events. From this analysis, we identified that the DNA repair and cell cycle pathways were overrepresented within the conserved mis-spliced transcript sets. In parallel, to functionally define pathways essential for survival and proliferation Srsf2P95H/+ cells, we performed a genome-wide pooled CRISPR loss of function screen using Hoxb8 immortalised R26-CreERki/+ Srsf2P95H/+ and R26-CreERki/+ Srsf2+/+ cell lines. We assessed for loss of sgRNA representation at three timepoints: immediately after Srsf2P95H/+ activation, and at one week and two weeks post Srsf2P95H/+ mutation. Pathway analysis demonstrated that the DNA damage response and cell cycle pathways were amongst the top synthetic lethal pathways with Srsf2P95H/+ mutation., Based on the loss of guide RNAs targeting Cdk6, we identified that Palbocilib, a CDK6 inhibitor, showed preferential sensitivity in Srsf2P95H/+ cell lines and in primary non-immortalised lin-cKIT+Sca-1+ cells compared to wild type controls. Our data strongly suggest that cell cycle and DNA damage response pathways are required for Srsf2P95H/+ cell survival, and that Palbociclib could be an alternative therapeutic option for targeting SRSF2 mutant myeloid cancers.

2021-09-15 | GSE165505 | GEO

Synthetic lethal and resistance interactions with BET bromodomain inhibitors [CRISPR screen]

Project description:Synthetic lethal and resistance interactions with BET bromodomain inhibitors [CRISPR screen]

| PRJNA542642 | ENA

Synthetic lethal siRNA screen for TN-IBC cell line SUM149PT using kinome library with EPA treatment

Project description:Synthetic lethal siRNA screen using a kinome library containing 939 druggable genes in the TN-IBC cell line SUM149PT, in combination with EPA treatment.

2019-01-31 | GSE102057 | GEO

Genome-wide synthetic lethal CRISPR screen identifies FIS1 as a genetic interactor of ALS-linked C9ORF72

Project description:Mutations in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis (ALS). Both toxic gain of function and loss of function pathogenic mechanisms have been proposed. Accruing evidence from mouse knockout studies point to a role for C9ORF72 as a regulator of immune function. To provide further insight into its cellular function, we performed a genome-wide synthetic lethal CRISPR screen in human myeloid cells lacking C9ORF72. We discovered a strong synthetic lethal genetic interaction between C9ORF72 and FIS1, which encodes a mitochondrial membrane protein involved in mitochondrial fission and mitophagy. Mass spectrometry experiments revealed that in C9ORF72 knockout cells, FIS1 strongly bound to a class of immune regulators that activate the receptor for advanced glycation end (RAGE) products and trigger inflammatory cascades. These findings present a novel genetic interactor for C9ORF72 and suggest a compensatory role for FIS1 in suppressing inflammatory signaling in the absence of C9ORF72.

2019-12-23 | GSE142504 | GEO

Kinome and Rho-GTPase Synthetic Lethal shRNA Library Screen in paired NF1-/- and GAP-Related Domain Restored Schwann Cells

Project description:To identify possible novel targets for the treatment of plexiform neurofibroma formation through a synthetic lethal shRNA library screen in the tumorigenic cell of origin, Schwann cells.

2019-11-30 | E-MTAB-8398 | biostudies-arrayexpress

Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7

Project description:Synthetic lethal CRISPR screen in MCF10A FBXW7 isogenic models

2023-05-22 | E-MTAB-12939 | biostudies-arrayexpress

Kinome-wide shRNA screen for synthetic lethality in patient-derived FANCA-deficient fibroblasts.

Project description:The purpose of this screen was to identify synthetic lethal targets in FANCA-deficient cells.

2021-05-24 | E-MTAB-9802 | biostudies-arrayexpress

CRISPR-Cas9 RBM10 synthetic lethality screen

Project description:CRISPR-Cas9 RBM10 synthetic lethality screen

| PRJEB60386 | ENA

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [CRISPR]

Project description:Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [CRISPR]

| PRJNA1002299 | ENA

Synthetic lethal screen reveals selective vulnerability of ATRX-mutant cancers to WEE1 inhibition

Project description:we performed a genome-wide synthetic lethal screen, using CRISPR-Cas9 genome editing, to identify potential therapeutic targets specific for ATRX-mutated cancers. In isogenic hepatocellular carcinoma (HCC) cell lines engineered for ATRX loss, we identified 58 genes, including the checkpoint kinase WEE1, uniquely required for the cell growth of ATRX null cells. Treatment with the WEE1 inhibitor AZD1775 robustly inhibited the growth of several ATRX-deficient HCC cell lines in vitro, as well as xenografts in vivo. The increased sensitivity to the WEE1 inhibitor was caused by accumulated DNA damage induced apoptosis. AZD1775 also selectively inhibited the proliferation of patient-derived primary cell lines from gliomas with naturally occurring ATRX mutations, indicating that the synthetic lethal relationship between WEE1 and ATRX could be exploited in a broader spectrum of human tumors. As WEE1 inhibitors have been investigated in several phase II clinical trials, our discovery provides the basis for an easily clinically testable therapeutic strategy specific for cancers deficient in ATRX.

2019-10-23 | GSE114035 | 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