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Fig 1.

Overview of the CMCL-DDI framework.

It comprises three main components: (a) graph view module, which encodes pharmacophore-level structural features using a Transformer-based encoder and readout function. Each pharmacophore box corresponds to the subgraphs decomposed from a single molecule; (b) sequence view module, which extracts semantic representations from SMILES strings using MOLBERT; and (c) cross-view contrastive learning module, which aligns the representations from both views during training. (d) DDI prediction module, which fuses the learned representations via a cross-attention mechanism and predicts interaction probability using a multi-layer perceptron.

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Fig 2.

The architecture of transformer.

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Table 1.

Hyperparameter configurations of model experiments.

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Table 2.

Confusion matrix for prediction results.

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Table 3.

The performance of CMCL-DDI and baselines on two datasets in the warm-start setting (%).

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Fig 3.

Performance comparison of different models under warm-start setting.

The left figure displays results on the DrugBank dataset, and the right figure shows results on the Twosides dataset.

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Table 4.

The performance of CMCL-DDI and baselines on two datasets in the cold-start setting (%).

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Fig 4.

Performance comparison of different models under cold-start setting.

The left figure displays results on the DrugBank dataset, and the right figure shows results on the Twosides dataset.

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Table 5.

Ablation study performance of CMCL-DDI.

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Fig 5.

Sensitivity analysis on the dimension of feature embeddings.

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Fig 6.

Sensitivity analysis of the number of attention heads.

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Fig 7.

Case studies demonstrating pharmacophores identified by CMCL-DDI in clinically confirmed DDIs.

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