Predicting the toxic side effects of drug interactions using chemical structures and protein sequences

Abstract The study aims to address the critical issue of toxic side effects resulting from drug combinations, which can significantly increase health risks, clinical complications, and lead to drug being withdrawn from the market. A model named TSEDDI (toxic side effects of drug-drug interaction) ha...

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Main Authors: Liyuan Zhang, Yongxin Sheng, Jinxiang Yang, Zuhai Hu, Bin Peng
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-82981-9
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author Liyuan Zhang
Yongxin Sheng
Jinxiang Yang
Zuhai Hu
Bin Peng
author_facet Liyuan Zhang
Yongxin Sheng
Jinxiang Yang
Zuhai Hu
Bin Peng
author_sort Liyuan Zhang
collection DOAJ
description Abstract The study aims to address the critical issue of toxic side effects resulting from drug combinations, which can significantly increase health risks, clinical complications, and lead to drug being withdrawn from the market. A model named TSEDDI (toxic side effects of drug-drug interaction) has been developed to improve the identification of drug pairs that may induce toxicity or adverse reactions. By utilizing drug chemical structures and diverse proteins, we employ a convolutional neural network (CNN) to extract features from molecular images, enzyme proteins, transporter proteins, and target proteins. Furthermore, we introduce a weighted binary cross entropy loss function to tackle class imbalance and integrate the multi-head attention mechanism with residual connections to enhance model performance. Our model outperformed advanced baseline models in predicting drug-drug interaction (DDI) side effects, achieving an accuracy of 0.9059 (± 0.0010) and consistently excelling across various evaluation metrics. The case study confirms the potential mechanisms by which four pairs of drugs cause side effects, thus demonstrating the effectiveness of our model in predicting DDI side effects. The TSEDDI model combines multiple attention mechanisms and residual connections, enhancing its ability to detect toxic and adverse effects related to DDIs. As a result, it becomes a valuable resource for promptly identifying adverse reactions in clinical trials. Future research could investigate drug substructures prone to toxic side effects.
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issn 2045-2322
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spelling doaj-art-2dc4c993398a4e5a9df256eded9af6bf2024-12-29T12:27:15ZengNature PortfolioScientific Reports2045-23222024-12-0114111210.1038/s41598-024-82981-9Predicting the toxic side effects of drug interactions using chemical structures and protein sequencesLiyuan Zhang0Yongxin Sheng1Jinxiang Yang2Zuhai Hu3Bin Peng4School of Public Health, Chongqing Medical UniversitySchool of Public Health, Chongqing Medical UniversitySchool of Public Health, Chongqing Medical UniversitySchool of Public Health, Chongqing Medical UniversitySchool of Public Health, Chongqing Medical UniversityAbstract The study aims to address the critical issue of toxic side effects resulting from drug combinations, which can significantly increase health risks, clinical complications, and lead to drug being withdrawn from the market. A model named TSEDDI (toxic side effects of drug-drug interaction) has been developed to improve the identification of drug pairs that may induce toxicity or adverse reactions. By utilizing drug chemical structures and diverse proteins, we employ a convolutional neural network (CNN) to extract features from molecular images, enzyme proteins, transporter proteins, and target proteins. Furthermore, we introduce a weighted binary cross entropy loss function to tackle class imbalance and integrate the multi-head attention mechanism with residual connections to enhance model performance. Our model outperformed advanced baseline models in predicting drug-drug interaction (DDI) side effects, achieving an accuracy of 0.9059 (± 0.0010) and consistently excelling across various evaluation metrics. The case study confirms the potential mechanisms by which four pairs of drugs cause side effects, thus demonstrating the effectiveness of our model in predicting DDI side effects. The TSEDDI model combines multiple attention mechanisms and residual connections, enhancing its ability to detect toxic and adverse effects related to DDIs. As a result, it becomes a valuable resource for promptly identifying adverse reactions in clinical trials. Future research could investigate drug substructures prone to toxic side effects.https://doi.org/10.1038/s41598-024-82981-9Adverse DDI predictionMulti-head self-attention mechanismDeep learningFeature extraction
spellingShingle Liyuan Zhang
Yongxin Sheng
Jinxiang Yang
Zuhai Hu
Bin Peng
Predicting the toxic side effects of drug interactions using chemical structures and protein sequences
Scientific Reports
Adverse DDI prediction
Multi-head self-attention mechanism
Deep learning
Feature extraction
title Predicting the toxic side effects of drug interactions using chemical structures and protein sequences
title_full Predicting the toxic side effects of drug interactions using chemical structures and protein sequences
title_fullStr Predicting the toxic side effects of drug interactions using chemical structures and protein sequences
title_full_unstemmed Predicting the toxic side effects of drug interactions using chemical structures and protein sequences
title_short Predicting the toxic side effects of drug interactions using chemical structures and protein sequences
title_sort predicting the toxic side effects of drug interactions using chemical structures and protein sequences
topic Adverse DDI prediction
Multi-head self-attention mechanism
Deep learning
Feature extraction
url https://doi.org/10.1038/s41598-024-82981-9
work_keys_str_mv AT liyuanzhang predictingthetoxicsideeffectsofdruginteractionsusingchemicalstructuresandproteinsequences
AT yongxinsheng predictingthetoxicsideeffectsofdruginteractionsusingchemicalstructuresandproteinsequences
AT jinxiangyang predictingthetoxicsideeffectsofdruginteractionsusingchemicalstructuresandproteinsequences
AT zuhaihu predictingthetoxicsideeffectsofdruginteractionsusingchemicalstructuresandproteinsequences
AT binpeng predictingthetoxicsideeffectsofdruginteractionsusingchemicalstructuresandproteinsequences