Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chromosome 8p-engineering and CRISPR-Cas9 viability screening reveal increased metastatic capacity of liver cancer cells targetable by patient-specific synthetic lethality

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE220320 | GEO | 2023/12/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Chromosome 8p-engineering and CRISPR-Cas9 viability screening reveal increased metastatic capacity of liver cancer cells targetable by patient-specific synthetic lethality [Cas9]

Project description:Large-scale chromosomal aberrations are prevalent in human cancer but their functional effects remain poorly understood. We describe the establishment of chromosome-engineered hepatocellular carcinoma cell lines using a dual guided CRISPR-Cas9 genome editing strategy. A mega base-sized region on chromosome 8p (chr8p) was heterozygously deleted mimicking a frequently observed copy number alteration (CNA) of solid tumors. Using this unique model system, we delineated the functional consequences of chr8p loss and its impact on metastatic behavior and patient survival. We found that metastasis associated genes on chr8p act in concert to induce an aggressive and invasive phenotype characteristic for chr8p deleted tumors. The conjunction of engineered chromosome-scale CNAs and genome-wide CRISPR-Cas9 viability screenings served as a powerful tool for the discovery of novel synthetic lethal targets and vulnerabilities accompanying patient-specific copy number changes. Using this target identification strategy, we showed that chr8p deletion sensitizes tumor cells to targeting of the reactive oxygen sanitizing enzyme Nudix hydrolase 17 (NUDT17).

2023-12-27 | GSE220312 | GEO

Chromosome 8p-engineering and CRISPR-Cas9 viability screening reveal increased metastatic capacity of liver cancer cells targetable by patient-specific synthetic lethality [Th]

2023-12-27 | GSE220319 | GEO

Chromosome 8p engineering reveals increased metastatic potential targetable by patient-specific synthetic lethality in liver cancer.

Project description:Large-scale chromosomal aberrations are prevalent in human cancer, but their function remains poorly understood. We established chromosome-engineered hepatocellular carcinoma cell lines using CRISPR-Cas9 genome editing. A 33-mega-base pair region on chromosome 8p (chr8p) was heterozygously deleted, mimicking a frequently observed chromosomal deletion. Using this isogenic model system, we delineated the functional consequences of chr8p loss and its impact on metastatic behavior and patient survival. We found that metastasis-associated genes on chr8p act in concert to induce an aggressive and invasive phenotype characteristic for chr8p-deleted tumors. Genome-wide CRISPR-Cas9 viability screening in isogenic chr8p-deleted cells served as a powerful tool to find previously unidentified synthetic lethal targets and vulnerabilities accompanying patient-specific chromosomal alterations. Using this target identification strategy, we showed that chr8p deletion sensitizes tumor cells to targeting of the reactive oxygen sanitizing enzyme Nudix hydrolase 17. Thus, chromosomal engineering allowed for the identification of novel synthetic lethalities specific to chr8p loss of heterozygosity.

| S-EPMC10745716 | biostudies-literature

Chromosome 8p-engineering and CRISPR-Cas9 viability screening reveal increased metastatic capacity of liver cancer cells targetable by patient-specific synthetic lethality [Cas9]

Project description:Chromosome 8p-engineering and CRISPR-Cas9 viability screening reveal increased metastatic capacity of liver cancer cells targetable by patient-specific synthetic lethality [Cas9]

| PRJNA909623 | ENA

Chromosome 8p-engineering and CRISPR-Cas9 viability screening reveal increased metastatic capacity of liver cancer cells targetable by patient-specific synthetic lethality

Project description:Chromosome 8p-engineering and CRISPR-Cas9 viability screening reveal increased metastatic capacity of liver cancer cells targetable by patient-specific synthetic lethality

| PRJNA909626 | ENA

Chromosome 8p-engineering and CRISPR-Cas9 viability screening reveal increased metastatic capacity of liver cancer cells targetable by patient-specific synthetic lethality [Th]

| PRJNA909632 | ENA

CRISPR-Cas9 RBM10 synthetic lethality screen

Project description:Genome-wide CRISPR-Cas9 knockout screen using TKOv1 sgRNA library was performed in isogenic RBM10-proficient and RBM10-deficient HCC827 cells.

2023-03-04 | E-MTAB-12724 | biostudies-arrayexpress

Synthetic Lethality Screening with Recursive Feature Machines.

Project description:Synthetic lethality refers to a genetic interaction where the simultaneous perturbation of gene pairs leads to cell death. Synthetically lethal gene pairs (SL pairs) provide a potential avenue for selectively targeting cancer cells based on genetic vulnerabilities. The rise of large-scale gene perturbation screens such as the Cancer Dependency Map (DepMap) offers the opportunity to identify SL pairs automatically using machine learning. We build on a recently developed class of feature learning kernel machines known as Recursive Feature Machines (RFMs) to develop a pipeline for identifying SL pairs based on CRISPR viability data from DepMap. In particular, we first train RFMs to predict viability scores for a given CRISPR gene knockout from cell line embeddings consisting of gene expression and mutation features. After training, RFMs use a statistical operator known as average gradient outer product to provide weights for each feature indicating the importance of each feature in predicting cellular viability. We subsequently apply correlation-based filters to re-weight RFM feature importances and identify those features that are most indicative of low cellular viability. Our resulting pipeline is computationally efficient, taking under 3 minutes for analyzing all 17, 453 knockouts from DepMap for candidate SL pairs. We show that our pipeline more accurately recovers experimentally verified SL pairs than prior approaches. Moreover, our pipeline finds new candidate SL pairs, thereby opening novel avenues for identifying genetic vulnerabilities in cancer.

| S-EPMC10723282 | biostudies-literature

CRISPR-Cas9 RBM10 synthetic lethality screen

Project description:CRISPR-Cas9 RBM10 synthetic lethality screen

| PRJEB60386 | ENA

A requirement for STAG2 in replication fork progression creates a targetable synthetic lethality in cohesin-mutant cancers.

Project description:Cohesin is a multiprotein ring that is responsible for cohesion of sister chromatids and formation of DNA loops to regulate gene expression. Genomic analyses have identified that the cohesin subunit STAG2 is frequently inactivated by mutations in cancer. However, the reason STAG2 mutations are selected during tumorigenesis and strategies for therapeutically targeting mutant cancer cells are largely unknown. Here we show that STAG2 is essential for DNA replication fork progression, whereby STAG2 inactivation in non-transformed cells leads to replication fork stalling and collapse with disruption of interaction between the cohesin ring and the replication machinery as well as failure to establish SMC3 acetylation. As a consequence, STAG2 mutation confers synthetic lethality with DNA double-strand break repair genes and increased sensitivity to select cytotoxic chemotherapeutic agents and PARP or ATR inhibitors. These studies identify a critical role for STAG2 in replication fork procession and elucidate a potential therapeutic strategy for cohesin-mutant cancers.

| S-EPMC6459917 | biostudies-literature

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