In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19
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In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19Autor(es)
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2021-02-26Cita bibliográfica
López-Cortés A, Guevara-Ramírez P, Kyriakidis NC, Barba-Ostria C, León Cáceres Á, Guerrero S, Ortiz-Prado E, Munteanu CR, Tejera E, Cevallos-Robalino D, Gómez-Jaramillo AM, Simbaña-Rivera K, Granizo-Martínez A, Pérez-M G, Moreno S, García-Cárdenas JM, Zambrano AK, Pérez-Castillo Y, Cabrera-Andrade A, Puig San Andrés L, Proaño-Castro C, Bautista J, Quevedo A, Varela N, Quiñones LA and Paz-y-Miño C (2021) In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19. Front. Pharmacol. 12:598925. doi: 10.3389/fphar.2021.598925
Resumo
[Abstract] Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively.
Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19.
Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics.
Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at https://github.com/muntisa/immuno-drug-repurposing-COVID-19.
Palabras chave
COVID-19
Immune system
Single-cell RNA sequencing
Artificial neural networks
Drug repurposing
Immune system
Single-cell RNA sequencing
Artificial neural networks
Drug repurposing
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Dereitos
Atribución 4.0 Internacional Copyright © 2021 López-Cortés, Guevara-Ramírez, Kyriakidis, Barba-Ostria, León
Cáceres, Guerrero, Ortiz-Prado, Munteanu, Tejera, Cevallos-Robalino, Gómez-
Jaramillo, Simbaña-Rivera, Granizo-Martínez, Pérez-M, Moreno, García-
Cárdenas, Zambrano, Pérez-Castillo, Cabrera-Andrade, Puig San Andrés,
Proaño-Castro, Bautista, Quevedo, Varela, Quiñones and Paz-y-Miño. 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.
ISSN
1663-9812