Predicting potential treatments for complex diseases based on miRNA and tissue specificity

TL;DR

This paper introduces miTS, a novel computational method that predicts potential drug treatments for diseases by integrating miRNA data and tissue specificity, validated through breast cancer case studies.

Contribution

The study presents miTS, a new approach combining miRNA, drug, and disease data within tissue-specific networks to predict drug-disease relationships, including novel potential treatments.

Findings

83.3% of top-30 predicted drugs for breast cancer are known in CTD

Five new drugs predicted with supporting evidence from multiple analyses

Regorafenib identified as a promising candidate for breast cancer

Abstract

Drug repositioning, that is finding new uses for existing drugs to treat more patients. Cumulative studies demonstrate that the mature miRNAs as well as their precursors can be targeted by small molecular drugs. At the same time, human diseases result from the disordered interplay of tissue- and cell lineage-specific processes. However, few computational researches predict drug-disease potential relationships based on miRNA data and tissue specificity. Therefore, based on miRNA data and the tissue specificity of diseases, we propose a new method named as miTS to predict the potential treatments for diseases. Firstly, based on miRNAs data, target genes and information of FDA approved drugs, we evaluate the relationships between miRNAs and drugs in the tissue-specific PPI network. Then, we construct a tripartite network: drug-miRNA-disease Finally, we obtain the potential drug-disease associations based on the tripartite network. In this paper, we take breast cancer as case study and focus on the top-30 predicted drugs. 25 of them (83.3%) are found having known connections with breast cancer in CTD benchmark and the other 5 drugs are potential drugs for breast cancer. We further evaluate the 5 newly predicted drugs from clinical records, literature mining, KEGG pathways enrichment analysis and overlapping genes between enriched pathways. For each of the 5 new drugs, strongly supported evidences can be found in three or more aspects. In particular, Regorafenib has 15 overlapping KEGG pathways with breast cancer and their p-values are all very small. In addition, whether in the literature curation or clinical validation, Regorafenib has a strong correlation with breast cancer. All the facts show that Regorafenib is likely to be a truly effective drug, worthy of our further study. It further follows that our method miTS is effective and practical for predicting new drug indications.