Ontology highlight
ABSTRACT:
PROVIDER: PRJNA774158 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16559773.fastq.gz | Fastqsanger.gz |
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Project description:Anticancer chemotherapy is an essential part of cancer treatment, but the emergence of resistance remains a major hurdle. Metabolic reprogramming is a notable phenotype associated with the acquisition of drug resistance. Here, we develop a computational framework that predicts metabolic gene targets capable of reverting the metabolic state of drug-resistant cells to that of drug-sensitive parental cells, thereby sensitizing the resistant cells. The computational framework performs single-gene knockout simulation of genome-scale metabolic models that predicts genome-wide metabolic flux distribution in drug-resistant cells, and clusters the resulting knockout flux data using uniform manifold approximation and projection. From the clustering analysis, knockout genes that lead to the flux data near that of drug-sensitive cells are considered drug sensitization targets. This computational approach is demonstrated using doxorubicin- and paclitaxel-resistant MCF7 breast cancer cells. Drug sensitization targets are further refined based on proteome and metabolome data, which generate GOT1 for doxorubicin-resistant MCF7, GPI for paclitaxel-resistant MCF7, and SLC1A5 as a common target. These targets are experimentally validated where inhibiting their expression results in increased sensitivity of drug-resistant cells to doxorubicin or paclitaxel. Taken together, the computational framework predicts drug sensitization targets in an intuitive and cost-efficient manner and can be applied to overcome drug-resistant cells associated with various cancers and other metabolic diseases.
2025-04-30 | GSE288840 | GEO
Project description:This study involves a forward genetic screen to identify common insertion sites in drug resistant clones. We will be utilising piggybac transposon systems in order to generate multiple drug resistant clones in a range of human cancer cell lines.
| EGAD00001000980 | EGA
Project description:This study involves a forward genetic screen to identify common insertion sites in drug resistant clones. We will be utilising piggybac transposon systems in order to generate multiple drug resistant clones in a range of human cancer cell lines.
| EGAS00001000468 | EGA
Project description:Aims: Deubiquitinases (DUBs) are proteases with emerging roles in cancer progression and therapy resistance, yet their contribution to drug resistance in ovarian cancer remains underexplored. Ovarian cancer patients often fail to benefit from platinum-based therapy, highlighting the need to identify novel factors involved in drug resistance. To this end we performed a CRISPR/Cas9 screen targeting DUB family to identify genes essential for platinum- resistant ovarian carcinoma cell survival. Methods: A CRISPR/CAS9 DUB knockout screen was performed on IGROV-1 parental and platinum-resistant ovarian carcinoma cells. Preclinical pharmacology approaches were also applied. Results: We identified USP18 as a survival factor in platinum-resistant ovarian cancer cells. USP18 expression was elevated at the mRNA and protein levels across five platinum-resistant cell lines. Knockdown and CRISPR/CAS9 editing of USP18 sensitized cells to cisplatin, coinciding with impaired repair of cisplatin-induced DNA damage. RNA-seq of USP18 RNA interfered and edited cells revealed the modulation of pathways including DNA repair. A peptide-based USP18 inhibitor suppressed growth of resistant cells, supporting its role in sustaining the growth of platinum-resistant cells. Conclusion: We identified USP18 as a novel mediator of platinum resistance in ovarian cancer, through modulating DNA repair. Targeting USP18 may offer a therapeutic strategy to improve outcomes in platinum-resistant ovarian cancer.
2026-05-29 | GSE326132 | GEO
Project description:Chlamydia trachomatis is a prevalent bacterial cause of urogenital and ocular infections. The pathogen uses the effector CpoS to suppress a host defense response that aborts intracellular bacterial growth by inducing host cell death. We conducted a CRISPR knockout screen to identify host genes contributing to this response, thereby revealing modulators of C. trachomatis parasitophorous vacuole stability. In brief, we transduced HeLa cells, a human cervical epithelial cell line, with a genome-wide knockout library. More specifically, we used the Brunello sgRNA library (which targets 19,114 genes and comprises a total of 77,441 sgRNAs, including about four sgRNAs per gene and 1000 non-targeting control sgRNAs). An aliquot of the transduced cells was collected to determine the composition of the pre-selection cell population (= sample “Pre”). In the selection procedure, we infected transduced cells with C. trachomatis L2/434/Bu, either wildtype (CTL2) or a strain carrying an insertional disruption of cpoS (CTL2-cpoS::cat). Later, we collected cells resistant to infection-mediated killing, that is, cells resistant to late-stage lytic death in the case of CTL2 or premature death in the case of CTL2-cpoS::cat. Hence, we included four distinct conditions: uninfected cells and cells infected with CTL2-cpoS::cat collected at 30 hours post infection (samples “UI30h” and “KO30h”), and uninfected cells and cells infected with CTL2 collected at 60 hours post infection (samples “UI60h” and “WT60h”). The screen was performed in two independent replicates (R1+R2).
2025-07-10 | E-MTAB-15337 | biostudies-arrayexpress
Project description:This project is a drug-gene interaction dual-guide CRISPR screen using a 3-guide pairs per gene library design.
2025-02-12 | E-MTAB-13980 | biostudies-arrayexpress
Project description:This project is a drug-gene interaction CRISPR screen to compare a 3-guide and a 6-guide library.
2025-02-12 | E-MTAB-13979 | biostudies-arrayexpress
Project description:Introduction: Glioblastomas utilize malignant gene expression pathways to drive growth. Many of these gene pathways are not directly accessible with molecularly targeted pharmacological agents. Chromatin-modifying compounds can alter gene expression and target glioblastoma growth pathways. In this study, we utilize a systematic screen of chromatin-modifying compounds on a panel of patient-derived glioblastoma lines to identify promising compounds and their associated gene targets. Methods: Five glioblastoma cell lines were subjected to a drug screen of 106 chromatin-modifying compounds representing 36 unique drug classes to determine the twelve most promising drug classes and the best candidate inhibitors in each class. These twelve drugs were then tested with a panel of twelve patient-derived gliomasphere lines to identify growth inhibition and corresponding gene expression patterns. Overlap analysis and weighted co-expression network analysis (WCGNA) were utilized to determine potential target genes and gene pathways. Results: The initial drug screen identified twelve candidate pharmacologic agents for further testing. Drug sensitivity testing indicated an overall high degree of variability between gliomasphere lines. However, CPI203 was the most consistently effective compound, and the BET inhibitor class was the most consistently effective class of compounds across the gliomasphere panel. Correspondingly, most of the compounds tested had highly variable effects on gene expression between gliomasphere lines. CPI203 stood out as the only compound to induce a consistent effect on gene expression across different gliomasphere lines, specifically down-regulation of DNA-synthesis genes. Amongst the twelve tested cell lines, high expression of CDKN2A and CDKN2B distinguished more drug sensitive from more drug resistant lines. WCGNA identified two oncogenic gene modules (FBXO5 and MELK) that were effectively downregulated by CPI203 (FBXO5) and ML228 (FBXO5 and MELK). Conclusions: The bromodomain inhibitor CPI203 induced relatively consistent effects on gene expression and growth across a variety of glioblastoma lines, specifically down-regulating genes associated with DNA replication. We propose that clinically effective BET inhibitors have the potential to induce consistent beneficial effects across a spectrum of glioblastomas.
2025-03-06 | GSE290922 | GEO
Project description:To investigate the molecular mechanisms underlying acquired resistance to lenvatinib in hepatocellular carcinoma (HCC), we established a lenvatinib-resistant mouse model using H22 cell-based subcutaneous xenografts. Tumor tissues were collected from lenvatinib-sensitive (H22-NR) and lenvatinib-resistant (H22-LR) mice. We performed RNA-sequencing to identify differentially expressed genes and signaling pathways that mediate lenvatinib resistance. Comparative gene expression profiling analysis between the NR and LR groups was conducted to screen for key drivers of drug resistance.
2026-04-23 | GSE328515 | GEO
Project description:With the widespread of drug-resistant Mycobacterium tuberculosis (Mtb), anti-TB drugs with novel structures and targets are urgently needed to prevent the prevalence of drug-resistant strains. For the past few decades, many Mtb CYPs been structurally and functionally characterized, and some of them were proved to be potential drug targets. CYP138 belongs to the Mtb CYPs whose structures and functions are still unclear. In our study, to discover differentially expressed proteins, a cyp138-knockout strain was built, and the function of CYP138 was speculated by the comparison between cyp138-knockout and wild-type strains through 6-plex TMT-labeling-based quantitative proteomic approach.
2024-03-10 | PXD045505 | Pride