Cancer drug combination therapies offer a promising strategy to overcome resistance and improve treatment efficacy, but identifying synergistic drug pairs is challenging due to complex biological interactions and tumor heterogeneity. Current machine learning algorithms for drug synergy prediction primarily rely on large-scale, multimodal datasets, yet suffer from critical limitations including poor interpretability, difficulty distinguishing causative biological relationships from correlations, and inadequate modeling of cancer-specific molecular interactions. To address these challenges, we propose CASynergy (Causal Attention and Cross-attention Synergy), a novel deep learning model for predicting cancer drug synergy that addresses limitations of prior approaches in accuracy and interpretability. CASynergy introduces a causal attention mechanism to distinguish true causal genomic features from spurious correlations, cell line-specific gene network construction to capture the unique molecular context of each cancer cell line, and a cross-attention module to integrate drug molecular features with cell line gene expression profiles. These improvements allow CASynergy to clearly identify significant drug-gene interactions and provides interpretable insights into why a combination is predicted to be synergistic. Experiments on two benchmark datasets (DrugCombDB and Oncology-Screen) suggests that CASynergy outperformed five state-of-the-art models. CASynergy offers a better and more reliable way to predict effective drug combinations. It works well across different cancer types and is easier to understand, which is important for personalized cancer treatment and finding new drugs.

Synergistic drug combinations have shown promising results in treating cancer cell lines by enhancing therapeutic efficacy and minimizing adverse reactions. The effects of a drug vary across cell lines, and cell lines respond differently to various drugs during treatment. Recently, many AI-based techniques have been developed for predicting synergistic drug combinations. However, existing computational models have not addressed this phenomenon, neglecting the refinement of features for the same drug and cell line in different scenarios. In this work, we propose a feature refinement deep learning framework, termed FRSynergy, to identify synergistic drug combinations. It can guide the refinement of drug and cell line features in different scenarios by capturing relationships among diverse drug-drug-cell line triplet features and learning feature contextual information. The heterogeneous graph attention network is employed to acquire topological information-based original features for drugs and cell lines from sampled sub-graphs. Then, the feature refinement network is designed by combining attention mechanism and context information, which can learn context-aware feature representations for each drug and cell line feature in diverse drug-drug-cell line triplet contexts. Extensive experiments affirm the strong performance of FRSynergy in predicting synergistic drug combinations and, more importantly, demonstrate the effectiveness of feature refinement network in synergistic drug combination prediction.

Prediction of drug-target interactions (DTIs) is essential in medicine field, since it benefits the identification of molecular structures potentially interacting with drugs and facilitates the discovery and reposition of drugs. Recently, much attention has been attracted to network representation learning to learn rich information from heterogeneous data. Although network representation learning algorithms have achieved success in predicting DTI, several manually designed meta-graphs limit the capability of extracting complex semantic information. To address the problem, we introduce an adaptive meta-graph-based method, termed AMGDTI, for DTI prediction. In the proposed AMGDTI, the semantic information is automatically aggregated from a heterogeneous network by training an adaptive meta-graph, thereby achieving efficient information integration without requiring domain knowledge. The effectiveness of the proposed AMGDTI is verified on two benchmark datasets. Experimental results demonstrate that the AMGDTI method overall outperforms eight state-of-the-art methods in predicting DTI and achieves the accurate identification of novel DTIs. It is also verified that the adaptive meta-graph exhibits flexibility and effectively captures complex fine-grained semantic information, enabling the learning of intricate heterogeneous network topology and the inference of potential drug-target relationship.

Synergistic drug combination prediction tasks based on the computational models have been widely studied and applied in the cancer field. However, most of models only consider the interactions between drug pairs and specific cell lines, without taking into account the multiple biological relationships of drug-drug and cell line-cell line that also largely affect synergistic mechanisms. To this end, here we propose a multi-modal deep learning framework, termed MDNNSyn, which adequately applies multi-source information and trains multi-modal features to infer potential synergistic drug combinations. MDNNSyn extracts topology modality features by implementing the multi-layer hypergraph neural network on drug synergy hypergraph and constructs semantic modality features through similarity strategy. A multi-modal fusion network layer with gated neural network is then employed for synergy score prediction. MDNNSyn is compared to five classic and state-of-the-art prediction methods on DrugCombDB and Oncology-Screen datasets. The model achieves area under the curve (AUC) scores of 0.8682 and 0.9013 on two datasets, an improvement of 3.70 % and 2.71 % over the second-best model. Case study indicates that MDNNSyn is capable of detecting potential synergistic drug combinations.

Mild Cognitive Impairment (MCI) is a preclinical stage of Alzheimer's Disease (AD) and is clinical heterogeneity. The classification of MCI is crucial for the early diagnosis and treatment of AD. In this study, we investigated the potential of using both labeled and unlabeled samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to classify MCI through the multimodal co-training method. We utilized both structural magnetic resonance imaging (sMRI) data and genotype data of 364 MCI samples including 228 labeled and 136 unlabeled MCI samples from the ADNI-1 cohort. First, the selected quantitative trait (QT) features from sMRI data and SNP features from genotype data were used to build two initial classifiers on 228 labeled MCI samples. Then, the co-training method was implemented to obtain new labeled samples from 136 unlabeled MCI samples. Finally, the random forest algorithm was used to obtain a combined classifier to classify MCI patients in the independent ADNI-2 dataset. The experimental results showed that our proposed framework obtains an accuracy of 85.50 percent and an AUC of 0.825 for MCI classification, respectively, which showed that the combined utilization of sMRI and SNP data through the co-training method could significantly improve the performances of MCI classification.