A data-driven methodology towards evaluating the potential of drug repurposing hypotheses

Santamaría, Lucía Prieto; Carro, Esther Ugarte; Uzquiano, Marina Díaz; Ruiz, Ernestina Menasalvas; Gallardo, Yuliana Pérez; Rodríguez‐González, Alejandro

doi:10.1016/j.csbj.2021.08.003

Cited by 20 publications

(15 citation statements)

References 69 publications

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“…For non-rare diseases the data sources were predominantly three articles: Xue et al [25], Jarada et al [26], and Li and Jones [27]. This selection has been made based on a recent study where the selection of successful drug repositioning cases was further explored [16].…”

Section: Methodsmentioning

confidence: 99%

“…A great example of a computer-based approach to generating drug repositioning hypotheses can be seen in this paper [16], that has established a methodological pipeline that can generate new drug repositioning hypotheses by integrating biomedical knowledge. In this line, [17] shows an approach using a data-driven approach to determine several potential drugs that could be repositioned for COVID -19, showing the importance and the potential impact of these techniques.…”

Section: Related Workmentioning

confidence: 99%

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Drug repositioning with gender perspective focused on Adverse Drug Reactions

Otero-Carrasco

Perez

Menasalvas

et al. 2022

Preprint

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Drug repositioning is a novel, useful, and crucial technique to find new uses for existing drugs. In this field of study, when the clinical trials necessary to obtain successful drug repositioning have been carried out, the female gender has not been given much consideration. Thus far, the participation of women in clinical trials has been very limited. There were several argued reasons to exclude them from trials, like the likelihood of pregnancy or sudden hormonal changes. This has meant that for a long time the adverse effects of a drug on women were unknown. Scientifically, it was known that due to the biological processes of pharmacokinetics and pharmacodynamics, the response to drugs was not the same in both genders, but despite this evidence, there is still no difference in the dosage or form of using a drug between men and women. In this study, we made a preliminary analysis where the main goal is to investigate gender differences within the drug repositioning field through the adverse effects produced by such treatments. A special section on specific cases of drug repositioning in rare diseases will also be considered to carry out the same verification previously mentioned in the text.

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Section: Methodsmentioning

confidence: 99%

Section: Related Workmentioning

confidence: 99%

Drug repositioning with gender perspective focused on Adverse Drug Reactions

Otero-Carrasco

Perez

Menasalvas

et al. 2022

Preprint

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“…Screening Candidate Therapeutic Agents. The Connectivity Map (cMap) is an online database for exploring the relationship between molecule drugs, gene expressions, and diseases [26][27][28][29]. The above upregulated and downregulated DEGs screened by the limma package were entered into the cMap database and compared with the reference datasets.…”

Section: 7mentioning

confidence: 99%

Downregulation of MicroRNA-1 and Its Potential Molecular Mechanism in Nasopharyngeal Cancer: An Investigation Combined with In Silico and In-House Immunohistochemistry Validation

et al. 2022

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Background. This study was aimed at elucidating the molecular biological mechanisms of microRNA-1 (miR-1) in nasopharyngeal carcinoma (NPC). Method. In this study, we performed a pooled analysis of miR-1 expression data derived from public databases, such as GEO, ArrayExpress, TCGA, and GTEx. The miRWalk 2.0 database, combined with the mRNA microarray datasets, was used to screen the target genes, and the genes were then subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis using the DAVID 6.8 database. We then used the STRING 11.0 database and Cytoscape 3.80 software to construct a protein-protein interaction (PPI) network for screening hub genes. Immunohistochemistry (IHC) was further used to validate the expression of hub genes. Finally, potential therapeutic agents for NPC were screened by the Connectivity Map (cMap) database. Results. Pooled analysis showed that miR-1 expression was significantly decreased in NPC ( SMD = − 0.57 ; P < 0.05 ). The summary receiver operating characteristic curve suggested that miR-1 had a good ability to distinguish cancerous tissues from noncancerous tissues ( AUC = 0.78 ). The results of GO analysis focused on mitotic nuclear division, DNA replication, cell division, cell adhesion, extracellular space, kinesin complex, and extracellular matrix (ECM) structural constituent. The KEGG analysis suggested that the target genes played a role in key signaling pathways, such as cell cycle, focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, and PI3K/Akt signaling pathway. The PPI network suggested that cyclin-dependent kinase 1 (CDK1) was the hub gene, and the CDK1 protein was subsequently confirmed to be significantly upregulated in NPC tissues by IHC. Finally, potential therapeutic drugs, such as masitinib, were obtained by the cMap database. Conclusion. miR-1 may play a vital part in NPC tumorigenesis and progression by regulating focal adhesion kinase to participate in cell mitosis, regulating ECM degradation, and affecting the PI3K/Akt signaling pathway. miR-1 has the potential to be a therapeutic target for NPC.

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“…The progress in computer science and artificial intelligence is increasing exponentially, which has favoured the research on drug-repositioning processes using computational-based techniques over the years, having developed new hypotheses through them. One of the most remarkable advances in recent years has been the development of a new methodological pathway capable of producing potential new drug-repositioning hypotheses through integrated knowledge based on biomedicine [ 13 ]. Cancer is one of the diseases that has benefited most from these studies, which outline different potential therapies to treat this disease [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

et al. 2022

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Rare diseases are a group of uncommon diseases in the world population. To date, about 7000 rare diseases have been documented. However, most of them do not have a known treatment. As a result of the relatively low demand for their treatments caused by their scarce prevalence, the pharmaceutical industry has not sufficiently encouraged the research to develop drugs to treat them. This work aims to analyse potential drug-repositioning strategies for this kind of disease. Drug repositioning seeks to find new uses for existing drugs. In this context, it seeks to discover if rare diseases could be treated with medicines previously indicated to heal other diseases. Our approaches tackle the problem by employing computational methods that calculate similarities between rare and non-rare diseases, considering biological features such as genes, proteins, and symptoms. Drug candidates for repositioning will be checked against clinical trials found in the scientific literature. In this study, 13 different rare diseases have been selected for which potential drugs could be repositioned. By verifying these drugs in the scientific literature, successful cases were found for 75% of the rare diseases studied. The genetic associations and phenotypical features of the rare diseases were examined. In addition, the verified drugs were classified according to the anatomical therapeutic chemical (ATC) code to highlight the types with a higher predisposition to be repositioned. These promising results open the door for further research in this field of study.

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A data-driven methodology towards evaluating the potential of drug repurposing hypotheses

Abstract: Graphical abstract

Cited by 20 publications

References 69 publications

Drug repositioning with gender perspective focused on Adverse Drug Reactions

Drug repositioning with gender perspective focused on Adverse Drug Reactions

Downregulation of MicroRNA-1 and Its Potential Molecular Mechanism in Nasopharyngeal Cancer: An Investigation Combined with In Silico and In-House Immunohistochemistry Validation

Repositioning Drugs for Rare Diseases Based on Biological Features and Computational Approaches

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