Cargando…

Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning

Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health...

Descripción completa

Detalles Bibliográficos
Autores principales: Shameer, Khader, Glicksberg, Benjamin S, Hodos, Rachel, Johnson, Kipp W, Badgeley, Marcus A, Readhead, Ben, Tomlinson, Max S, O’Connor, Timothy, Miotto, Riccardo, Kidd, Brian A, Chen, Rong, Ma’ayan, Avi, Dudley, Joel T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192146/
https://www.ncbi.nlm.nih.gov/pubmed/28200013
http://dx.doi.org/10.1093/bib/bbw136
_version_ 1783363851448745984
author Shameer, Khader
Glicksberg, Benjamin S
Hodos, Rachel
Johnson, Kipp W
Badgeley, Marcus A
Readhead, Ben
Tomlinson, Max S
O’Connor, Timothy
Miotto, Riccardo
Kidd, Brian A
Chen, Rong
Ma’ayan, Avi
Dudley, Joel T
author_facet Shameer, Khader
Glicksberg, Benjamin S
Hodos, Rachel
Johnson, Kipp W
Badgeley, Marcus A
Readhead, Ben
Tomlinson, Max S
O’Connor, Timothy
Miotto, Riccardo
Kidd, Brian A
Chen, Rong
Ma’ayan, Avi
Dudley, Joel T
author_sort Shameer, Khader
collection PubMed
description Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. However, the rapid increase in drug development cost demands innovative and sustainable drug discovery approaches. Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development. As the number of drug repurposing investigations increases, a new opportunity has emerged to understand factors driving drug repositioning through systematic analyses of drugs, drug targets and associated disease indications. However, such analyses have so far been hampered by the lack of a centralized knowledgebase, benchmarking data sets and reporting standards. To address these knowledge and clinical needs, here, we present RepurposeDB, a collection of repurposed drugs, drug targets and diseases, which was assembled, indexed and annotated from public data. RepurposeDB combines information on 253 drugs [small molecules (74.30%) and protein drugs (25.29%)] and 1125 diseases. Using RepurposeDB data, we identified pharmacological (chemical descriptors, physicochemical features and absorption, distribution, metabolism, excretion and toxicity properties), biological (protein domains, functional process, molecular mechanisms and pathway cross talks) and epidemiological (shared genetic architectures, disease comorbidities and clinical phenotype similarities) factors mediating drug repositioning. Collectively, RepurposeDB is developed as the reference database for drug repositioning investigations. The pharmacological, biological and epidemiological principles of drug repositioning identified from the meta-analyses could augment therapeutic development.
format Online
Article
Text
id pubmed-6192146
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-61921462018-10-23 Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning Shameer, Khader Glicksberg, Benjamin S Hodos, Rachel Johnson, Kipp W Badgeley, Marcus A Readhead, Ben Tomlinson, Max S O’Connor, Timothy Miotto, Riccardo Kidd, Brian A Chen, Rong Ma’ayan, Avi Dudley, Joel T Brief Bioinform Paper Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. However, the rapid increase in drug development cost demands innovative and sustainable drug discovery approaches. Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development. As the number of drug repurposing investigations increases, a new opportunity has emerged to understand factors driving drug repositioning through systematic analyses of drugs, drug targets and associated disease indications. However, such analyses have so far been hampered by the lack of a centralized knowledgebase, benchmarking data sets and reporting standards. To address these knowledge and clinical needs, here, we present RepurposeDB, a collection of repurposed drugs, drug targets and diseases, which was assembled, indexed and annotated from public data. RepurposeDB combines information on 253 drugs [small molecules (74.30%) and protein drugs (25.29%)] and 1125 diseases. Using RepurposeDB data, we identified pharmacological (chemical descriptors, physicochemical features and absorption, distribution, metabolism, excretion and toxicity properties), biological (protein domains, functional process, molecular mechanisms and pathway cross talks) and epidemiological (shared genetic architectures, disease comorbidities and clinical phenotype similarities) factors mediating drug repositioning. Collectively, RepurposeDB is developed as the reference database for drug repositioning investigations. The pharmacological, biological and epidemiological principles of drug repositioning identified from the meta-analyses could augment therapeutic development. Oxford University Press 2017-02-15 /pmc/articles/PMC6192146/ /pubmed/28200013 http://dx.doi.org/10.1093/bib/bbw136 Text en © The Author 2016. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Paper
Shameer, Khader
Glicksberg, Benjamin S
Hodos, Rachel
Johnson, Kipp W
Badgeley, Marcus A
Readhead, Ben
Tomlinson, Max S
O’Connor, Timothy
Miotto, Riccardo
Kidd, Brian A
Chen, Rong
Ma’ayan, Avi
Dudley, Joel T
Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning
title Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning
title_full Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning
title_fullStr Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning
title_full_unstemmed Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning
title_short Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning
title_sort systematic analyses of drugs and disease indications in repurposedb reveal pharmacological, biological and epidemiological factors influencing drug repositioning
topic Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192146/
https://www.ncbi.nlm.nih.gov/pubmed/28200013
http://dx.doi.org/10.1093/bib/bbw136
work_keys_str_mv AT shameerkhader systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT glicksbergbenjamins systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT hodosrachel systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT johnsonkippw systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT badgeleymarcusa systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT readheadben systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT tomlinsonmaxs systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT oconnortimothy systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT miottoriccardo systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT kiddbriana systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT chenrong systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT maayanavi systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning
AT dudleyjoelt systematicanalysesofdrugsanddiseaseindicationsinrepurposedbrevealpharmacologicalbiologicalandepidemiologicalfactorsinfluencingdrugrepositioning