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Scientists Develop Accurate Drug Repositioning Method through Non-tissue Specific Core Signatures from Cancer Transcriptomes

Oct 10, 2018     Email"> PrintText Size

In recent years, drug repositioning is globally popular and plays an important role in pharmaceutical industry, which helps to discover new indications for existing drugs.

Along with large-scale omics data of drug treatment and genetic perturbation being released, computational biology and bioinformatics methods show a great advantage in integrating the various types of data for drug target identification and drug repositioning studies.  

However, to our knowledge, a high throughput strategy to reposition drugs in human with high precision is still challenging. In particular, pattern-matching tools cannot judge whether the similarities or differences stem from tissue-of-origin backgrounds or relevant/true drug-gene interactions (DGIs), while confining the searches to the same tissue or cell type will severely limits the number of drugs, genes or pathways that can be analyzed. 

A research team led by Prof. Jing-Dong Jackie Han from CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences constructed a new drug repositioning method using non-tissue specific core signatures from cancer transcriptomes.

The study proposes drug-gene modes of action inference and drug specificity assessment systems, and predicts 179,004 drug repositioning candidates for 1,938 specific drugs. 

In the study, researchers developed an in silico screen in human in vivo conditions using a reference of single gene mutations’ non-tissue specific "core transcriptome signatures" (CSs) of 8,476 genes generated from the TCGA database.

They developed "core-signature Drug-to-Gene" (csD2G) software to scan 3,546 drug treatment profiles against the reference signatures. csD2G significantly outperformed conventional cell line based gene perturbation signatures, L1000 signature based experimental drug-target prediction and existing drug repositioning methods in both coverage and specificity.  

This research entitled "Accurate Drug Reposition through Non-Tissue Specific Core Signatures from Cancer Transcriptomes" was published in Cell Reports on October 9th, 2018. 

The study was supported by grants from the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Chinese Academy of Sciences. 

 

Schematic illustration of drug repositioning method and application (Image by Prof. HAN's team)

(Editor: ZHANG Nannan)

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