Dataset Information

Predicting Drug-Induced Liver Injury Using Convolutional Neural Network and Molecular Fingerprint-Embedded Features.

ABSTRACT: As a critical issue in drug development and postmarketing safety surveillance, drug-induced liver injury (DILI) leads to failures in clinical trials as well as retractions of on-market approved drugs. Therefore, it is important to identify DILI compounds in the early-stages through in silico and in vivo studies. It is difficult using conventional safety testing methods, since the predictive power of most of the existing frameworks is insufficiently effective to address this pharmacological issue. In our study, we employ a natural language processing (NLP) inspired computational framework using convolutional neural networks and molecular fingerprint-embedded features. Our development set and independent test set have 1597 and 322 compounds, respectively. These samples were collected from previous studies and matched with established chemical databases for structural validity. Our study comes up with an average accuracy of 0.89, Matthews's correlation coefficient (MCC) of 0.80, and an AUC of 0.96. Our results show a significant improvement in the AUC values compared to the recent best model with a boost of 6.67%, from 0.90 to 0.96. Also, based on our findings, molecular fingerprint-embedded featurizer is an effective molecular representation for future biological and biochemical studies besides the application of classic molecular fingerprints.

SUBMITTER: Nguyen-Vo TH

PROVIDER: S-EPMC7542839 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Predicting Drug-Induced Liver Injury Using Convolutional Neural Network and Molecular Fingerprint-Embedded Features.

Nguyen-Vo Thanh-Hoang TH Nguyen Loc L Do Nguyet N Le Phuc H PH Nguyen Thien-Ngan TN Nguyen Binh P BP Le Ly L

ACS omega 20200922 39

As a critical issue in drug development and postmarketing safety surveillance, drug-induced liver injury (DILI) leads to failures in clinical trials as well as retractions of on-market approved drugs. Therefore, it is important to identify DILI compounds in the early-stages through in silico and in vivo studies. It is difficult using conventional safety testing methods, since the predictive power of most of the existing frameworks is insufficiently effective to address this pharmacological issue ...[more]

PMID: 33043223

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Project description:OBJECTIVES:To develop a proof-of-concept "interpretable" deep learning prototype that justifies aspects of its predictions from a pre-trained hepatic lesion classifier. METHODS:A convolutional neural network (CNN) was engineered and trained to classify six hepatic tumor entities using 494 lesions on multi-phasic MRI, described in Part 1. A subset of each lesion class was labeled with up to four key imaging features per lesion. A post hoc algorithm inferred the presence of these features in a test set of 60 lesions by analyzing activation patterns of the pre-trained CNN model. Feature maps were generated that highlight regions in the original image that correspond to particular features. Additionally, relevance scores were assigned to each identified feature, denoting the relative contribution of a feature to the predicted lesion classification. RESULTS:The interpretable deep learning system achieved 76.5% positive predictive value and 82.9% sensitivity in identifying the correct radiological features present in each test lesion. The model misclassified 12% of lesions. Incorrect features were found more often in misclassified lesions than correctly identified lesions (60.4% vs. 85.6%). Feature maps were consistent with original image voxels contributing to each imaging feature. Feature relevance scores tended to reflect the most prominent imaging criteria for each class. CONCLUSIONS:This interpretable deep learning system demonstrates proof of principle for illuminating portions of a pre-trained deep neural network's decision-making, by analyzing inner layers and automatically describing features contributing to predictions. KEY POINTS:• An interpretable deep learning system prototype can explain aspects of its decision-making by identifying relevant imaging features and showing where these features are found on an image, facilitating clinical translation. • By providing feedback on the importance of various radiological features in performing differential diagnosis, interpretable deep learning systems have the potential to interface with standardized reporting systems such as LI-RADS, validating ancillary features and improving clinical practicality. • An interpretable deep learning system could potentially add quantitative data to radiologic reports and serve radiologists with evidence-based decision support.

Project description:PurposeAccurate segmentation of liver and liver tumors is critical for radiotherapy. Liver tumor segmentation, however, remains a difficult and relevant problem in the field of medical image processing because of the various factors like complex and variable location, size, and shape of liver tumors, low contrast between tumors and normal tissues, and blurred or difficult-to-define lesion boundaries. In this paper, we proposed a neural network (S-Net) that can incorporate attention mechanisms to end-to-end segmentation of liver tumors from CT images.MethodsFirst, this study adopted a classical coding-decoding structure to realize end-to-end segmentation. Next, we introduced an attention mechanism between the contraction path and the expansion path so that the network could encode a longer range of semantic information in the local features and find the corresponding relationship between different channels. Then, we introduced long-hop connections between the layers of the contraction path and the expansion path, so that the semantic information extracted in both paths could be fused. Finally, the application of closed operation was used to dissipate the narrow interruptions and long, thin divide. This eliminated small cavities and produced a noise reduction effect.ResultsIn this paper, we used the MICCAI 2017 liver tumor segmentation (LiTS) challenge dataset, 3DIRCADb dataset and doctors' manual contours of Hubei Cancer Hospital dataset to test the network architecture. We calculated the Dice Global (DG) score, Dice per Case (DC) score, volumetric overlap error (VOE), average symmetric surface distance (ASSD), and root mean square error (RMSE) to evaluate the accuracy of the architecture for liver tumor segmentation. The segmentation DG for tumor was found to be 0.7555, DC was 0.613, VOE was 0.413, ASSD was 1.186 and RMSE was 1.804. For a small tumor, DG was 0.3246 and DC was 0.3082. For a large tumor, DG was 0.7819 and DC was 0.7632.ConclusionS-Net obtained more semantic information with the introduction of an attention mechanism and long jump connection. Experimental results showed that this method effectively improved the effect of tumor recognition in CT images and could be applied to assist doctors in clinical treatment.

Dataset Information

Predicting Drug-Induced Liver Injury Using Convolutional Neural Network and Molecular Fingerprint-Embedded Features.

Publications

Predicting Drug-Induced Liver Injury Using Convolutional Neural Network and Molecular Fingerprint-Embedded Features.

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