Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparison
Abstract Ubiquitin-specific-processing protease 7 (USP7) is a promising target protein for cancer therapy, and great attention has been given to the identification of USP7 inhibitors. Traditional virtual screening methods have now been successfully applied to discover USP7 inhibitors aiming at reduc...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Cheminformatics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13321-022-00675-8 |
| _version_ | 1797952383940034560 |
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| author | Wen-feng Shen He-wei Tang Jia-bo Li Xiang Li Si Chen |
| author_facet | Wen-feng Shen He-wei Tang Jia-bo Li Xiang Li Si Chen |
| author_sort | Wen-feng Shen |
| collection | DOAJ |
| description | Abstract Ubiquitin-specific-processing protease 7 (USP7) is a promising target protein for cancer therapy, and great attention has been given to the identification of USP7 inhibitors. Traditional virtual screening methods have now been successfully applied to discover USP7 inhibitors aiming at reducing costs and speeding up time in several studies. However, due to their unsatisfactory accuracy, it is still a difficult task to develop USP7 inhibitors. In this study, multiple supervised learning classifiers were built to distinguish active USP7 inhibitors from inactive ligands. Physicochemical descriptors, MACCS keys, ECFP4 fingerprints and SMILES were first calculated to represent the compounds in our in-house dataset. Two deep learning (DL) models and nine classical machine learning (ML) models were then constructed based on different combinations of the above molecular representations under three activity cutoff values, and a total of 15 groups of experiments (75 experiments) were implemented. The performance of the models in these experiments was evaluated, compared and discussed using a variety of metrics. The optimal models are ensemble learning models when the dataset is balanced or severely imbalanced, and SMILES-based DL performs the best when the dataset is slightly imbalanced. Meanwhile, multimodal data fusion in some cases can improve the performance of ML and DL models. In addition, SMOTE, unbiased decoy selection and SMILES enumeration can improve the performance of ML and DL models when the dataset is severely imbalanced, and SMOTE works the best. Our study established highly accurate supervised learning classification models, which would accelerate the development of USP7 inhibitors. Some guidance was also provided for drug researchers in selecting supervised models and molecular representations as well as handling imbalanced datasets. Graphical Abstract |
| first_indexed | 2024-04-10T22:46:35Z |
| format | Article |
| id | doaj.art-f009b12afb704153b9920019a28a9aff |
| institution | Directory Open Access Journal |
| issn | 1758-2946 |
| language | English |
| last_indexed | 2024-04-10T22:46:35Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cheminformatics |
| spelling | doaj.art-f009b12afb704153b9920019a28a9aff2023-01-15T12:20:09ZengBMCJournal of Cheminformatics1758-29462023-01-0115111610.1186/s13321-022-00675-8Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparisonWen-feng Shen0He-wei Tang1Jia-bo Li2Xiang Li3Si Chen4School of Medicine & School of Computer Engineering and Science, Shanghai UniversitySchool of Medicine & School of Computer Engineering and Science, Shanghai UniversitySchool of Medicine & School of Computer Engineering and Science, Shanghai UniversitySchool of Pharmacy, Second Military Medical UniversitySchool of Medicine & School of Computer Engineering and Science, Shanghai UniversityAbstract Ubiquitin-specific-processing protease 7 (USP7) is a promising target protein for cancer therapy, and great attention has been given to the identification of USP7 inhibitors. Traditional virtual screening methods have now been successfully applied to discover USP7 inhibitors aiming at reducing costs and speeding up time in several studies. However, due to their unsatisfactory accuracy, it is still a difficult task to develop USP7 inhibitors. In this study, multiple supervised learning classifiers were built to distinguish active USP7 inhibitors from inactive ligands. Physicochemical descriptors, MACCS keys, ECFP4 fingerprints and SMILES were first calculated to represent the compounds in our in-house dataset. Two deep learning (DL) models and nine classical machine learning (ML) models were then constructed based on different combinations of the above molecular representations under three activity cutoff values, and a total of 15 groups of experiments (75 experiments) were implemented. The performance of the models in these experiments was evaluated, compared and discussed using a variety of metrics. The optimal models are ensemble learning models when the dataset is balanced or severely imbalanced, and SMILES-based DL performs the best when the dataset is slightly imbalanced. Meanwhile, multimodal data fusion in some cases can improve the performance of ML and DL models. In addition, SMOTE, unbiased decoy selection and SMILES enumeration can improve the performance of ML and DL models when the dataset is severely imbalanced, and SMOTE works the best. Our study established highly accurate supervised learning classification models, which would accelerate the development of USP7 inhibitors. Some guidance was also provided for drug researchers in selecting supervised models and molecular representations as well as handling imbalanced datasets. Graphical Abstracthttps://doi.org/10.1186/s13321-022-00675-8Machine learningDeep learningMolecular representationsMultimodal data fusionUbiquitin-specific-processing protease 7 |
| spellingShingle | Wen-feng Shen He-wei Tang Jia-bo Li Xiang Li Si Chen Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparison Journal of Cheminformatics Machine learning Deep learning Molecular representations Multimodal data fusion Ubiquitin-specific-processing protease 7 |
| title | Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparison |
| title_full | Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparison |
| title_fullStr | Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparison |
| title_full_unstemmed | Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparison |
| title_short | Multimodal data fusion for supervised learning-based identification of USP7 inhibitors: a systematic comparison |
| title_sort | multimodal data fusion for supervised learning based identification of usp7 inhibitors a systematic comparison |
| topic | Machine learning Deep learning Molecular representations Multimodal data fusion Ubiquitin-specific-processing protease 7 |
| url | https://doi.org/10.1186/s13321-022-00675-8 |
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