Medicine
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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Chapters
Summary December 11th, 2016
Here we describe a protocol using the web-based drug repurposing hypothesis generation tool: "RE:fine Drugs." This protocol can be modified to a user's preferences at the level of the query type (gene, drug or disease) and/or the range of available advanced options.
Transcript
The overall goal of this software tool is to generate and prioritize drug repurposing hypothesis based on both genome-wide association study data and phenome-wide association study data. This method can help answer questions in the drug discovery field, including which available drugs can be repurposed when you use disease indications and which candidates have more support in the literature. The main advantage of this technique is that multiple entry points are available to explore the repurposing potential whether it be from the perspective of specific disease, gene, or drug.
Access the home page for RE:fine Drugs. Begin by entering a query term in the search bar. This term can be a generic drug name, a new disease indication or a gene.
Filter the search bar function to include only drug name, new disease indication, gene symbol, or all categories. The search bar includes an autofill function for query entries. Put in a keyword and click on the Search button.
The table of results can be stored by multiple options as listed in the top row. Navigate to the advanced search option to enable the drug information feature. Click on icon in the Info column for a particular drug.
Observe a page that list the P-Value for the association, disease name, drug name gene details, and drug details. Click on the Advanced button located on the right side of page in several options to further refine the results provided. The advanced search options include modifications to drug, association, disease, potential, gene, and action.
Export the results tables by clicking on the Export button on the right side of the page. Click on the Simple button to pull down the advanced search window. Under the advanced option drug tab, specify a particular drug indication or an additional drug name to filter the results.
Click on the association tab to filter the results by the significance level P-Value, adjusted P-Value with false discovery rate, effect size, and/or study type. Under the disease tab, specify a certain disease description for the predicted new use. Within the potential tab, filter the results according to wether the drug indication is contained in the DrugBank database, the number of medline abstracts with co-occurence of the drug and the disease, the number of ClinicalTrials.
gov database entries with this co-occurrence, as well as the repurposing potential. Under the gene tab, enter a single-nucleotide polymorphism identifier or gene symbol to filter the results by specific drug target genes. Click on the action tab and specify the drug action type against the drug target as either agonist, antagonist, other, unknown, or all.
In this example, the gene IL2RB was entered as a gene-based query and 12 drug repurposing hypotheses for the IL2RB gene are returned. The detailed information page for a particular drug repurposing hypothesis is provided from the info column. Shown here are only those drugs with a known indication for the transplant disease term.
The association tab allows the user to filter SNP phenotype relationships by statistical significance and by genetic effect size. Genetic effect size is defined as the odds of the presence of disease in individuals with the specific genotype over the odds in individuals without the SNP allele. The results under the potential tab can be filtered by a minimum number of five medline abstracts containing a co-occurrence of drug and disease terms.
In this example, all drug results under the gene tab are targeted for the IL2RB gene corresponding to the original query term. Finally, results filtered as agonists under the action tab return all drugs that act as agonists on the IL2RB gene. After watching this video, you should have a good understanding of how to use the RE:fine Drugs tool to generate and prioritize drug repurposing hypothesis.
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