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Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases

Repurposing is an increasingly attractive method within the field of drug development for its efficiency at identifying new therapeutic opportunities among approved drugs at greatly reduced cost and time of more traditional methods. Repurposing has generated significant interest in the realm of rare...

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Autores principales: Challa, Anup P., Zaleski, Nicole M., Jerome, Rebecca N., Lavieri, Robert R., Shirey-Rice, Jana K., Barnado, April, Lindsell, Christopher J., Aronoff, David M., Crofford, Leslie J., Harris, Raymond C., Alp Ikizler, T., Mayer, Ingrid A., Holroyd, Kenneth J., Pulley, Jill M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355705/
https://www.ncbi.nlm.nih.gov/pubmed/34394194
http://dx.doi.org/10.3389/fgene.2021.707836
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author Challa, Anup P.
Zaleski, Nicole M.
Jerome, Rebecca N.
Lavieri, Robert R.
Shirey-Rice, Jana K.
Barnado, April
Lindsell, Christopher J.
Aronoff, David M.
Crofford, Leslie J.
Harris, Raymond C.
Alp Ikizler, T.
Mayer, Ingrid A.
Holroyd, Kenneth J.
Pulley, Jill M.
author_facet Challa, Anup P.
Zaleski, Nicole M.
Jerome, Rebecca N.
Lavieri, Robert R.
Shirey-Rice, Jana K.
Barnado, April
Lindsell, Christopher J.
Aronoff, David M.
Crofford, Leslie J.
Harris, Raymond C.
Alp Ikizler, T.
Mayer, Ingrid A.
Holroyd, Kenneth J.
Pulley, Jill M.
author_sort Challa, Anup P.
collection PubMed
description Repurposing is an increasingly attractive method within the field of drug development for its efficiency at identifying new therapeutic opportunities among approved drugs at greatly reduced cost and time of more traditional methods. Repurposing has generated significant interest in the realm of rare disease treatment as an innovative strategy for finding ways to manage these complex conditions. The selection of which agents should be tested in which conditions is currently informed by both human and machine discovery, yet the appropriate balance between these approaches, including the role of artificial intelligence (AI), remains a significant topic of discussion in drug discovery for rare diseases and other conditions. Our drug repurposing team at Vanderbilt University Medical Center synergizes machine learning techniques like phenome-wide association study—a powerful regression method for generating hypotheses about new indications for an approved drug—with the knowledge and creativity of scientific, legal, and clinical domain experts. While our computational approaches generate drug repurposing hits with a high probability of success in a clinical trial, human knowledge remains essential for the hypothesis creation, interpretation, “go-no go” decisions with which machines continue to struggle. Here, we reflect on our experience synergizing AI and human knowledge toward realizable patient outcomes, providing case studies from our portfolio that inform how we balance human knowledge and machine intelligence for drug repurposing in rare disease.
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spelling pubmed-83557052021-08-12 Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases Challa, Anup P. Zaleski, Nicole M. Jerome, Rebecca N. Lavieri, Robert R. Shirey-Rice, Jana K. Barnado, April Lindsell, Christopher J. Aronoff, David M. Crofford, Leslie J. Harris, Raymond C. Alp Ikizler, T. Mayer, Ingrid A. Holroyd, Kenneth J. Pulley, Jill M. Front Genet Genetics Repurposing is an increasingly attractive method within the field of drug development for its efficiency at identifying new therapeutic opportunities among approved drugs at greatly reduced cost and time of more traditional methods. Repurposing has generated significant interest in the realm of rare disease treatment as an innovative strategy for finding ways to manage these complex conditions. The selection of which agents should be tested in which conditions is currently informed by both human and machine discovery, yet the appropriate balance between these approaches, including the role of artificial intelligence (AI), remains a significant topic of discussion in drug discovery for rare diseases and other conditions. Our drug repurposing team at Vanderbilt University Medical Center synergizes machine learning techniques like phenome-wide association study—a powerful regression method for generating hypotheses about new indications for an approved drug—with the knowledge and creativity of scientific, legal, and clinical domain experts. While our computational approaches generate drug repurposing hits with a high probability of success in a clinical trial, human knowledge remains essential for the hypothesis creation, interpretation, “go-no go” decisions with which machines continue to struggle. Here, we reflect on our experience synergizing AI and human knowledge toward realizable patient outcomes, providing case studies from our portfolio that inform how we balance human knowledge and machine intelligence for drug repurposing in rare disease. Frontiers Media S.A. 2021-07-28 /pmc/articles/PMC8355705/ /pubmed/34394194 http://dx.doi.org/10.3389/fgene.2021.707836 Text en Copyright © 2021 Challa, Zaleski, Jerome, Lavieri, Shirey-Rice, Barnado, Lindsell, Aronoff, Crofford, Harris, Alp Ikizler, Mayer, Holroyd and Pulley. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Challa, Anup P.
Zaleski, Nicole M.
Jerome, Rebecca N.
Lavieri, Robert R.
Shirey-Rice, Jana K.
Barnado, April
Lindsell, Christopher J.
Aronoff, David M.
Crofford, Leslie J.
Harris, Raymond C.
Alp Ikizler, T.
Mayer, Ingrid A.
Holroyd, Kenneth J.
Pulley, Jill M.
Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases
title Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases
title_full Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases
title_fullStr Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases
title_full_unstemmed Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases
title_short Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases
title_sort human and machine intelligence together drive drug repurposing in rare diseases
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355705/
https://www.ncbi.nlm.nih.gov/pubmed/34394194
http://dx.doi.org/10.3389/fgene.2021.707836
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