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

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

PROVIDER: PRJNA1265765 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33649844_1.fastq.gz	Fastqsanger.gz
	SRR33649844_2.fastq.gz	Fastqsanger.gz
	SRR33649845_1.fastq.gz	Fastqsanger.gz
	SRR33649845_2.fastq.gz	Fastqsanger.gz

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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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Project description:The some biomarkers can be found by pairwise comparison. They can distinguish between extremely severe Hand,foot and mouth disease and mild Hand,foot and mouth disease,moreover,they can applied to diagnose extremely severe Hand,foot and mouth disease mild Hand,foot and mouth disease vs.control; extremely severe Hand,foot and mouth disease vs.control; extremely severe Hand,foot and mouth disease vs.mild Hand,foot and mouth disease,verification by qRT-PCR

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