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Systematically Prioritizing Candidates in Genome-Based Drug Repurposing

Drug repurposing is the application of approved drugs to treat diseases separate and distinct from their original indications. Herein, we define the scope of all practical precision drug repurposing using DrugBank, a publicly available database of pharmacological agents, and BioVU, a large, de-ident...

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Autores principales: Challa, Anup P., Lavieri, Robert R., Lewis, Judith T., Zaleski, Nicole M., Shirey-Rice, Jana K., Harris, Paul A., Aronoff, David M., Pulley, Jill M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921094/
https://www.ncbi.nlm.nih.gov/pubmed/31769998
http://dx.doi.org/10.1089/adt.2019.950
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author Challa, Anup P.
Lavieri, Robert R.
Lewis, Judith T.
Zaleski, Nicole M.
Shirey-Rice, Jana K.
Harris, Paul A.
Aronoff, David M.
Pulley, Jill M.
author_facet Challa, Anup P.
Lavieri, Robert R.
Lewis, Judith T.
Zaleski, Nicole M.
Shirey-Rice, Jana K.
Harris, Paul A.
Aronoff, David M.
Pulley, Jill M.
author_sort Challa, Anup P.
collection PubMed
description Drug repurposing is the application of approved drugs to treat diseases separate and distinct from their original indications. Herein, we define the scope of all practical precision drug repurposing using DrugBank, a publicly available database of pharmacological agents, and BioVU, a large, de-identified DNA repository linked to longitudinal electronic health records at Vanderbilt University Medical Center. We present a method of repurposing candidate prioritization through integration of pharmacodynamic and marketing variables from DrugBank with quality control thresholds for genomic data derived from the DNA samples within BioVU. Through the synergy of delineated “target-action pairs,” along with target genomics, we identify ∼230 “pairs” that represent all practical opportunities for genomic drug repurposing. From this analysis, we present a pipeline of 14 repurposing candidates across 7 disease areas that link to our repurposability platform and present high potential for randomized controlled trial startup in upcoming months.
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spelling pubmed-69210942019-12-23 Systematically Prioritizing Candidates in Genome-Based Drug Repurposing Challa, Anup P. Lavieri, Robert R. Lewis, Judith T. Zaleski, Nicole M. Shirey-Rice, Jana K. Harris, Paul A. Aronoff, David M. Pulley, Jill M. Assay Drug Dev Technol Original Articles Drug repurposing is the application of approved drugs to treat diseases separate and distinct from their original indications. Herein, we define the scope of all practical precision drug repurposing using DrugBank, a publicly available database of pharmacological agents, and BioVU, a large, de-identified DNA repository linked to longitudinal electronic health records at Vanderbilt University Medical Center. We present a method of repurposing candidate prioritization through integration of pharmacodynamic and marketing variables from DrugBank with quality control thresholds for genomic data derived from the DNA samples within BioVU. Through the synergy of delineated “target-action pairs,” along with target genomics, we identify ∼230 “pairs” that represent all practical opportunities for genomic drug repurposing. From this analysis, we present a pipeline of 14 repurposing candidates across 7 disease areas that link to our repurposability platform and present high potential for randomized controlled trial startup in upcoming months. Mary Ann Liebert, Inc., publishers 2019-12-01 2019-12-13 /pmc/articles/PMC6921094/ /pubmed/31769998 http://dx.doi.org/10.1089/adt.2019.950 Text en © Anup P. Challa et al. 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Challa, Anup P.
Lavieri, Robert R.
Lewis, Judith T.
Zaleski, Nicole M.
Shirey-Rice, Jana K.
Harris, Paul A.
Aronoff, David M.
Pulley, Jill M.
Systematically Prioritizing Candidates in Genome-Based Drug Repurposing
title Systematically Prioritizing Candidates in Genome-Based Drug Repurposing
title_full Systematically Prioritizing Candidates in Genome-Based Drug Repurposing
title_fullStr Systematically Prioritizing Candidates in Genome-Based Drug Repurposing
title_full_unstemmed Systematically Prioritizing Candidates in Genome-Based Drug Repurposing
title_short Systematically Prioritizing Candidates in Genome-Based Drug Repurposing
title_sort systematically prioritizing candidates in genome-based drug repurposing
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921094/
https://www.ncbi.nlm.nih.gov/pubmed/31769998
http://dx.doi.org/10.1089/adt.2019.950
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