Literature-Wide Association Studies (LWAS) for a Rare Disease: Drug Repurposing for Inflammatory Breast Cancer.

Xiaojia Ji,Xialan Dong,Maria S Dixon,Weifan Zheng,Chunming Jin,Kevin P Williams

doi:10.3390/molecules25173933

Xiaojia Ji, Xialan Dong + Show 4 more

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https://doi.org/10.3390/molecules25173933

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Abstract

Drug repurposing is an effective means for rapid drug discovery. The aim of this study was to develop and validate a computational methodology based on Literature-Wide Association Studies (LWAS) of PubMed to repurpose existing drugs for a rare inflammatory breast cancer (IBC). We have developed a methodology that conducted LWAS based on the text mining technology Word2Vec. 3.80 million “cancer”-related PubMed abstracts were processed as the corpus for Word2Vec to derive vector representation of biological concepts. These vectors for drugs and diseases served as the foundation for creating similarity maps of drugs and diseases, respectively, which were then employed to find potential therapy for IBC. Three hundred and thirty-six (336) known drugs and three hundred and seventy (370) diseases were expressed as vectors in this study. Nine hundred and seventy (970) previously known drug-disease association pairs among these drugs and diseases were used as the reference set. Based on the hypothesis that similar drugs can be used against similar diseases, we have identified 18 diseases similar to IBC, with 24 corresponding known drugs proposed to be the repurposing therapy for IBC. The literature search confirmed most known drugs tested for IBC, with four of them being novel candidates. We conclude that LWAS based on the Word2Vec technology is a novel approach to drug repurposing especially useful for rare diseases.

Highlights

There are multiple approaches to identifying a new drug
This finding based on Literature-Wide Association Studies (LWAS) that inflammatory breast cancer (IBC) and breast cancer cluster differently was consistent with a recent review that provided an overview of the unique clinical and molecular characteristics of IBC, and that IBC should be considered as a separate entity from non-IBC breast cancer [26]
The Literature-Wide Association Study (LWAS) based on Word2Vec technology is a plausible approach to drug repurposing for rare or understudied diseases

Summary

Introduction

There are multiple approaches to identifying a new drug. Virtual screening methods, including those based on quantitative structure-activity relationship (QSAR). Modeling and molecular docking, play a crucial part in the drug discovery process [2] These methods require either a training set of a fair number of known compounds and their biological activity against a relevant assay for QSAR modeling or 3D (3-dimensional) structures of drug targets for molecular docking studies, which may not always be feasible in rare disease research. To tackle drug discovery in these difficult situations, a complementary strategy called drug repurposing has been proposed that aims to identify and validate new uses for existing or developmental drugs that are outside the scope of the original medical indication [3,4,5]. Due to the fast growth of bioinformatics and chemical biology databases, this strategy has become a less risky, more rapid, and lower cost approach compared to Molecules 2020, 25, 3933; doi:10.3390/molecules25173933 www.mdpi.com/journal/molecules

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