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ABSTRACT: CRISPR/Cas9-based Drug Target Screening Library

PROVIDER: PRJNA1119749 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29274502_1.fastq.gz	Fastqsanger.gz
	SRR29274502_2.fastq.gz	Fastqsanger.gz
	SRR29274503_1.fastq.gz	Fastqsanger.gz
	SRR29274503_2.fastq.gz	Fastqsanger.gz
	SRR29274504_1.fastq.gz	Fastqsanger.gz

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Project description:CRISPR/Cas9-based Drug Target Screening Library 3

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Genome-wide CRISPR/Cas9 library screening identified OGDH as a regulator of disease progress and HMAs-resistance in MDS by reprogramming glutamine metabolism

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CRISPR Screening in Glioblastoma

Project description:This is an in vitro genome-wide CRISPR/cas9 screen in human glioblastoma stem cells, screening for genes essential for survival of these cells. These cells express cas9 and have been transfected with a guide RNA library causing gene knockouts. We will analyse the sequencing data for depletion of guide RNAs. In this particular study, we will do RNA sequencing to correlate CRISPR with expression levels in specific cancer cell subpopulations. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

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A Dual-Filter Strategy Integrating CRISPR-based Target Screening and Text Mining for Hand-Foot Syndrome

Project description:The experimental high-throughput screening (HTS) methods, exemplified by CRISPR-based screening, have revolutionized target identification in drug discovery. However, such screens frequently yield extensive and unrelated target lists necessitating costly and time-intensive experimental validation. Here, we propose a dual-filter strategy that integrates literature-mined targets with CRISPR/Cas9 screening outputs, systematically prioritizing the most credible candidates and thereby reducing the experimental validation burden and increasing success rate. To validate this strategy, we applied it with hand-foot syndrome (HFS), a clinically challenging side effect induced by fluoropyrimidine treatment. We identified ATF4 as a key regulator of 5-fluorouracil (5-FU) toxicity in the skin and revealed forskolin as a potential therapeutic agent of HFS through the strategy. Mechanistically, forskolin triggers MEK/ERK-dependent ATF4 induction, subsequently driving 5-FU detoxification via the ATF4-mediated eIF2α/IκB signaling pathway. Our findings demonstrate that this dual-filter strategy could notably accelerate drug discovery by reducing experimental validation burden after target screening.

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Genome-wide CRISPR-Cas9 screen in isogenic parental and RBM10-KO HCC827 cells

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

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CRISPR-Cas9 RBM10 synthetic lethality screen

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Project description:To minimize the human genome-wide CRISPR/Cas9 library size, we established H-mLib which recruited a novel sgRNA design method and applied with dual plasmid based strategy. The performance of the H-mLib was benchmarked to other CRISPR libraries in a proliferation screening conducted in K562 cells. We also identified human core essential genes and cell-type specific essentials genes in K562 and Jurkat cells.

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Project description:To search for factors regulating paternally imprinted genes (PEGs), we performed a genome-wide loss-of-function CRISPR/Cas9 screen in haploid parthenogenetic ESCs. This by staining a pooled CRISPR library with a PEG10 antibody and next FACS-sorted for cells that presented de-novo PEG10 expression.

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