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UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning

Drug-target interaction (DTI) prediction through in vitro methods is expensive and time-consuming. On the other hand, computational methods can save time and money while enhancing drug discovery efficiency. Most of the computational methods frame DTI prediction as a binary classification task. One i...

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Autores principales: Tayebi, Aida, Yousefi, Niloofar, Yazdani-Jahromi, Mehdi, Kolanthai, Elayaraja, Neal, Craig J., Seal, Sudipta, Garibay, Ozlem Ozmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100109/
https://www.ncbi.nlm.nih.gov/pubmed/35566330
http://dx.doi.org/10.3390/molecules27092980
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author Tayebi, Aida
Yousefi, Niloofar
Yazdani-Jahromi, Mehdi
Kolanthai, Elayaraja
Neal, Craig J.
Seal, Sudipta
Garibay, Ozlem Ozmen
author_facet Tayebi, Aida
Yousefi, Niloofar
Yazdani-Jahromi, Mehdi
Kolanthai, Elayaraja
Neal, Craig J.
Seal, Sudipta
Garibay, Ozlem Ozmen
author_sort Tayebi, Aida
collection PubMed
description Drug-target interaction (DTI) prediction through in vitro methods is expensive and time-consuming. On the other hand, computational methods can save time and money while enhancing drug discovery efficiency. Most of the computational methods frame DTI prediction as a binary classification task. One important challenge is that the number of negative interactions in all DTI-related datasets is far greater than the number of positive interactions, leading to the class imbalance problem. As a result, a classifier is trained biased towards the majority class (negative class), whereas the minority class (interacting pairs) is of interest. This class imbalance problem is not widely taken into account in DTI prediction studies, and the few previous studies considering balancing in DTI do not focus on the imbalance issue itself. Additionally, they do not benefit from deep learning models and experimental validation. In this study, we propose a computational framework along with experimental validations to predict drug-target interaction using an ensemble of deep learning models to address the class imbalance problem in the DTI domain. The objective of this paper is to mitigate the bias in the prediction of DTI by focusing on the impact of balancing and maintaining other involved parameters at a constant value. Our analysis shows that the proposed model outperforms unbalanced models with the same architecture trained on the BindingDB both computationally and experimentally. These findings demonstrate the significance of balancing, which reduces the bias towards the negative class and leads to better performance. It is important to note that leaning on computational results without experimentally validating them and by relying solely on AUROC and AUPRC metrics is not credible, particularly when the testing set remains unbalanced.
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spelling pubmed-91001092022-05-14 UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning Tayebi, Aida Yousefi, Niloofar Yazdani-Jahromi, Mehdi Kolanthai, Elayaraja Neal, Craig J. Seal, Sudipta Garibay, Ozlem Ozmen Molecules Article Drug-target interaction (DTI) prediction through in vitro methods is expensive and time-consuming. On the other hand, computational methods can save time and money while enhancing drug discovery efficiency. Most of the computational methods frame DTI prediction as a binary classification task. One important challenge is that the number of negative interactions in all DTI-related datasets is far greater than the number of positive interactions, leading to the class imbalance problem. As a result, a classifier is trained biased towards the majority class (negative class), whereas the minority class (interacting pairs) is of interest. This class imbalance problem is not widely taken into account in DTI prediction studies, and the few previous studies considering balancing in DTI do not focus on the imbalance issue itself. Additionally, they do not benefit from deep learning models and experimental validation. In this study, we propose a computational framework along with experimental validations to predict drug-target interaction using an ensemble of deep learning models to address the class imbalance problem in the DTI domain. The objective of this paper is to mitigate the bias in the prediction of DTI by focusing on the impact of balancing and maintaining other involved parameters at a constant value. Our analysis shows that the proposed model outperforms unbalanced models with the same architecture trained on the BindingDB both computationally and experimentally. These findings demonstrate the significance of balancing, which reduces the bias towards the negative class and leads to better performance. It is important to note that leaning on computational results without experimentally validating them and by relying solely on AUROC and AUPRC metrics is not credible, particularly when the testing set remains unbalanced. MDPI 2022-05-06 /pmc/articles/PMC9100109/ /pubmed/35566330 http://dx.doi.org/10.3390/molecules27092980 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tayebi, Aida
Yousefi, Niloofar
Yazdani-Jahromi, Mehdi
Kolanthai, Elayaraja
Neal, Craig J.
Seal, Sudipta
Garibay, Ozlem Ozmen
UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning
title UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning
title_full UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning
title_fullStr UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning
title_full_unstemmed UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning
title_short UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning
title_sort unbiaseddti: mitigating real-world bias of drug-target interaction prediction by using deep ensemble-balanced learning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100109/
https://www.ncbi.nlm.nih.gov/pubmed/35566330
http://dx.doi.org/10.3390/molecules27092980
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