Avoid non-diagnostic EUS-FNA: a DNN model as a possible gatekeeper to distinguish pancreatic lesions prone to inconclusive biopsy.

OBJECTIVE: This work aimed to explore the utility of CT radiomics with machine learning for distinguishing the pancreatic lesions prone to non-diagnostic ultrasound-guided fine-needle aspiration (EUS-FNA). METHODS: 498 patients with pancreatic EUS-FNA were retrospectively reviewed [Development cohort: 147 pancreatic ductal adenocarcinoma (PDAC); Validation cohort: 37 PDAC]. Pancreatic lesions not PDAC were also tested exploratively. Radiomics extracted from contrast-enhanced CT was integrated with deep neural networks (DNN) after dimension reduction. The receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were performed for model evaluation. And, the explainability of the DNN model was analyzed by integrated gradients. RESULTS: The DNN model was effective in distinguishing PDAC lesions prone to non-diagnostic EUS-FNA (Development cohort: AUC = 0.821, 95% CI: 0.742-0.900; Validation cohort: AUC = 0.745, 95% CI: 0.534-0.956). In all cohorts, the DNN model showed better utility than the logistic model based on traditional lesion characteristics with NRI >0 (p < 0.05). And, the DNN model had net benefits of 21.6% at the risk threshold of 0.60 in the validation cohort. As for the model explainability, gray-level co-occurrence matrix (GLCM) features contributed the most averagely and the first-order features were the most important in the sum attribution. CONCLUSION: The CT radiomics-based DNN model can be a useful auxiliary tool for distinguishing the pancreatic lesions prone to nondiagnostic EUS-FNA and provide alerts for endoscopists preoperatively to reduce unnecessary EUS-FNA. ADVANCES IN KNOWLEDGE: This is the first investigation into the utility of CT radiomics-based machine learning in avoiding non-diagnostic EUS-FNA for patients with pancreatic masses and providing potential pre-operative assistance for endoscopists.

Deep learning identifies explainable reasoning paths of mechanism of action for drug repurposing from multilayer biological network.

The discovery and repurposing of drugs require a deep understanding of the mechanism of drug action (MODA). Existing computational methods mainly model MODA with the protein-protein interaction (PPI) network. However, the molecular interactions of drugs in the human body are far beyond PPIs. Additionally, the lack of interpretability of these models hinders their practicability. We propose an interpretable deep learning-based path-reasoning framework (iDPath) for drug discovery and repurposing by capturing MODA on by far the most comprehensive multilayer biological network consisting of the complex high-dimensional molecular interactions between genes, proteins and chemicals. Experiments show that iDPath outperforms state-of-the-art machine learning methods on a general drug repurposing task. Further investigations demonstrate that iDPath can identify explicit critical paths that are consistent with clinical evidence. To demonstrate the practical value of iDPath, we apply it to the identification of potential drugs for treating prostate cancer and hypertension. Results show that iDPath can discover new FDA-approved drugs. This research provides a novel interpretable artificial intelligence perspective on drug discovery.

Ureteral calculi lithotripsy for single ureteral calculi: can DNN-assisted model help preoperatively predict risk factors for sepsis?

OBJECTIVES: To explore the utility of radiomics and deep learning model in assessing the risk factors for sepsis after flexible ureteroscopy lithotripsy (FURL) or percutaneous nephrolithotomy (PCNL) in patients with ureteral calculi. METHODS: This retrospective analysis included 847 patients with treatment-naive proximal ureteral calculi who received FURL or PCNL. All participants were preoperatively conducted non-contrast computed tomography scans, and relevant clinical information was meanwhile collected. After propensity score matching, the radiomics model was established to predict the onset of sepsis. A deep learning model was also adapted to further improve the prediction accuracy. Performance of these trained models was verified in another independent external validation set including 40 cases of ureteral calculi patients. RESULTS: The overall incidence of sepsis after FURL or PCNL was 5.9%. The least absolute shrinkage and selection operator (LASSO) regression analysis revealed 26 predictive variables, with an overall AUC of 0.881 (95% CI, 0.813-0.931) and an AUC of 0.783 (95% CI, 0.766-0.801) in external validation cohort. Judicious adaption of a deep neural network (DNN) model to our dataset improved the AUC to 0.920 (95% CI, 0.906-0.933) in the internal validation. To eliminate the overfitting, external validation was carried out for DNN model (AUC = 0.874 (95% CI, 0.858-0.891)). CONCLUSIONS: The DNN was more effective than the LASSO model in revealing risk factors for sepsis after FURL or PCNL in single ureteral calculi patients, and females are more susceptible to sepsis than males. Deep learning models have the potential to act as gatekeepers to facilitate patient stratification. KEY POINTS: • Both the least absolute shrinkage and selection operator (LASSO) and deep neural network (DNN) models were shown to be effective in sepsis prediction. • The DNN model achieved superior prediction capability, with an AUC of 0.920 (95% CI, 0.906-0.933). • DNN-assisted model has potential to serve as a gatekeeper to facilitate patient stratification.

GraphSynergy: a network-inspired deep learning model for anticancer drug combination prediction.

OBJECTIVE: To develop an end-to-end deep learning framework based on a protein-protein interaction (PPI) network to make synergistic anticancer drug combination predictions. MATERIALS AND METHODS: We propose a deep learning framework named Graph Convolutional Network for Drug Synergy (GraphSynergy). GraphSynergy adapts a spatial-based Graph Convolutional Network component to encode the high-order topological relationships in the PPI network of protein modules targeted by a pair of drugs, as well as the protein modules associated with a specific cancer cell line. The pharmacological effects of drug combinations are explicitly evaluated by their therapy and toxicity scores. An attention component is also introduced in GraphSynergy, which aims to capture the pivotal proteins that play a part in both PPI network and biomolecular interactions between drug combinations and cancer cell lines. RESULTS: GraphSynergy outperforms the classic and state-of-the-art models in predicting synergistic drug combinations on the 2 latest drug combination datasets. Specifically, GraphSynergy achieves accuracy values of 0.7553 (11.94% improvement compared to DeepSynergy, the latest published drug combination prediction algorithm) and 0.7557 (10.95% improvement compared to DeepSynergy) on DrugCombDB and Oncology-Screen datasets, respectively. Furthermore, the proteins allocated with high contribution weights during the training of GraphSynergy are proved to play a role in view of molecular functions and biological processes, such as transcription and transcription regulation. CONCLUSION: The introduction of topological relations between drug combination and cell line within the PPI network can significantly improve the capability of synergistic drug combination identification.