Novel artificial intelligence-based identification of drug-gene-disease interaction through using protein-protein interaction

Taguchi, Y.-h.; Turki, T.

doi:10.1101/2024.06.01.596984

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bioRxiv · 10.1101/2024.06.01.596984

Novel artificial intelligence-based identification of drug-gene-disease interaction through using protein-protein interaction

Taguchi, Y.-h.·Turki, T.

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Abstract

The evaluation of drug-gene-disease interactions is key for the identification of drugs effective against disease. However, at present, drugs that are effective against genes that are critical for disease are difficult to identify. Following a disease-centric approach, there is a need to identify genes critical to disease function and find drugs that are effective against them. By contrast, following a drug-centric approach comprises identifying the genes targeted by drugs, and then the diseases in which the identified genes are critical. Both of these processes are complex. Using a gene-centric approach, whereby we identify genes that are effective against the disease and can be targeted by drugs, is much easier. However, how such sets of genes can be identified without specifying either the target diseases or drugs is not known. In this study, a novel artificial intelligencebased approach that employs unsupervised methods and identifies genes without specifying neither diseases nor drugs is presented. To evaluate its feasibility, we applied tensor decomposition (TD)-based unsupervised feature extraction (FE) to perform drug repositioning from protein-protein interactions (PPI) without any other information. Proteins selected by TD-based unsupervised FE include many genes related to cancers, as well as drugs that target the selected proteins. Thus, we were able to identify cancer drugs using only PPI. Because the selected proteins had more interactions, we replaced the selected proteins with hub proteins and found that hub proteins themselves could be used for drug repositioning. In contrast to hub proteins, which can only identify cancer drugs, TD-based unsupervised FE enables the identification of drugs for other diseases. In addition, TD-based unsupervised FE can be used to identify drugs that are effective in in vivo experiments, which is difficult when hub proteins are used. In conclusion, TD-based unsupervised FE is a useful tool for drug repositioning using only PPI without other information.

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Taguchi, Y.-h., Turki, T.. 2024-06-03. Novel artificial intelligence-based identification of drug-gene-disease interaction through using protein-protein interaction. https://doi.org/10.1101/2024.06.01.596984

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