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A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

ABSTRACT: A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

PROVIDER: PRJNA747256 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15175478_1.fastq.gz	Fastqsanger.gz
	SRR15175478_2.fastq.gz	Fastqsanger.gz
	SRR15175479_1.fastq.gz	Fastqsanger.gz
	SRR15175479_2.fastq.gz	Fastqsanger.gz
	SRR15175480_1.fastq.gz	Fastqsanger.gz

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A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer (liver cancer cell lines)

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A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

Project description:We first treated LX-2 cells with vehicle or HHT (1μM and 5μM) for 6 hours. Then, RNA sequencing was conducted to quantify the mRNA expression level of vehicle-treated or HHT-treated LX-2 cells. HHT-induced expression changes were obtained based on the resultant data.

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A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer.

Project description:Pharmacologic perturbation projects, such as Connectivity Map (CMap) and Library of Integrated Network-based Cellular Signatures (LINCS), have produced many perturbed expression data, providing enormous opportunities for computational therapeutic discovery. However, there is no consensus on which methodologies and parameters are the most optimal to conduct such analysis. Aiming to fill this gap, new benchmarking standards were developed to quantitatively evaluate drug retrieval performance. Investigations of potential factors influencing drug retrieval were conducted based on these standards. As a result, we determined an optimal approach for LINCS data-based therapeutic discovery. With this approach, homoharringtonine (HHT) was identified to be a candidate agent with potential therapeutic and preventive effects on liver cancer. The antitumor and antifibrotic activity of HHT was validated experimentally using subcutaneous xenograft tumor model and carbon tetrachloride (CCL4)-induced liver fibrosis model, demonstrating the reliability of the prediction results. In summary, our findings will not only impact the future applications of LINCS data but also offer new opportunities for therapeutic intervention of liver cancer.

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Alterations in soybean gene expression profile after foliar application of lipo-chitooligosaccharide (LCO) from Bradyrhizobium japonicum under sub-optimal temperature

Project description:Lipo-chitooligosaccharides (LCOs) produced by N2-fixing rhizobacteria initiate host nodule formation. Foliar application of LCOs has been shown to induce stress-related genes under optimal growth conditions. To study the effects of LCO foliar spray under stressed conditions, soybean seedlings grown at optimal temperature were exposed to sub-optimal temperature. After a 5-day acclimation period, the first trifoliolate leaves were sprayed with 10-7 M LCO (NodBj-V (C18:1, MeFuc)) produced by Bradyrhizobium japonicum, and harvested at 0 and 48 h following treatment. Microarray analysis was performed using Affymetrix GeneChipÂ® Soybean Genome Arrays. A total of 147 genes were differentially expressed 48 h after LCO treatment, including a number of stress-related genes and transcription factors. In addition, during the 48 h following treatment, hundreds of genes were differentially expressed in LCO-treated plants, indicating that the dynamic soybean foliar transcriptome was highly responsive to LCO treatment. The microarray data was supported by quantitative real-time PCR data. Soybean seedlings grown at optimal temperature (25 Â°C) were exposed to sub-optimal temperature (15 Â°C). After a 5-day acclimation period, the first trifoliolate leaves were sprayed with 10-7 M LCO (NodBj-V (C18:1, MeFuc)) produced by Bradyrhizobium japonicum, and harvested at 0 and 48 h following treatment. Total RNA was extracted and microarray analysis was performed using Affymetrix GeneChipÂ® Soybean Genome Arrays.

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