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Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections

Introduction: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp., commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited effi...

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Autores principales: Rivara-Espasandín, Martin, Palumbo, Miranda Clara, Sosa, Ezequiel J., Radío, Santiago, Turjanski, Adrián G., Sotelo-Silveira, José, Fernandez Do Porto, Dario, Smircich, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115950/
https://www.ncbi.nlm.nih.gov/pubmed/37089958
http://dx.doi.org/10.3389/fphar.2023.1136321
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author Rivara-Espasandín, Martin
Palumbo, Miranda Clara
Sosa, Ezequiel J.
Radío, Santiago
Turjanski, Adrián G.
Sotelo-Silveira, José
Fernandez Do Porto, Dario
Smircich, Pablo
author_facet Rivara-Espasandín, Martin
Palumbo, Miranda Clara
Sosa, Ezequiel J.
Radío, Santiago
Turjanski, Adrián G.
Sotelo-Silveira, José
Fernandez Do Porto, Dario
Smircich, Pablo
author_sort Rivara-Espasandín, Martin
collection PubMed
description Introduction: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp., commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches. Methods: In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development. Results and Discussion: Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery.
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spelling pubmed-101159502023-04-21 Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections Rivara-Espasandín, Martin Palumbo, Miranda Clara Sosa, Ezequiel J. Radío, Santiago Turjanski, Adrián G. Sotelo-Silveira, José Fernandez Do Porto, Dario Smircich, Pablo Front Pharmacol Pharmacology Introduction: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp., commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches. Methods: In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development. Results and Discussion: Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery. Frontiers Media S.A. 2023-04-06 /pmc/articles/PMC10115950/ /pubmed/37089958 http://dx.doi.org/10.3389/fphar.2023.1136321 Text en Copyright © 2023 Rivara-Espasandín, Palumbo, Sosa, Radío, Turjanski, Sotelo-Silveira, Fernandez Do Porto and Smircich. 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 Pharmacology
Rivara-Espasandín, Martin
Palumbo, Miranda Clara
Sosa, Ezequiel J.
Radío, Santiago
Turjanski, Adrián G.
Sotelo-Silveira, José
Fernandez Do Porto, Dario
Smircich, Pablo
Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections
title Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections
title_full Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections
title_fullStr Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections
title_full_unstemmed Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections
title_short Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections
title_sort omics data integration facilitates target selection for new antiparasitic drugs against tritryp infections
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115950/
https://www.ncbi.nlm.nih.gov/pubmed/37089958
http://dx.doi.org/10.3389/fphar.2023.1136321
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