Synthetic lethality (SL) offers a promising approach for targeted anti-cancer therapy. Deeply understanding SL gene pair mechanisms is vital for anti-cancer drug discovery. However, current wet-lab and machine learning-based SL prediction methods lack user-friendly and quantitatively evaluable explanations. To address these problems, we propose a prompt-based pipeline for generating natural language explanations. We first construct a natural language dataset named NexLeth. This dataset is derived from New Bing through prompt-based queries and expert annotations and contains 707 instances. NexLeth enhances the understanding of SL mechanisms and it is a benchmark for evaluating SL explanation methods. For the task of natural language generation for SL explanations, we combine subgraph explanations from an SL knowledge graph (KG) with instructions to construct novel personalized prompts, so as to inject the domain knowledge into the generation process. We then leverage the prompts to fine-tune pre-trained biomedical language models on our dataset. Experimental results show that the fine-tuned model equipped with designed prompts performs better than existing biomedical language models in terms of text quality and explainability, suggesting the potential of our dataset and the fine-tuned model for generating understandable and reliable explanations of SL mechanisms.

Contrastive learning is emerging as a powerful technique for extracting knowledge from unlabeled data. This technique requires a balanced mixture of two ingredients: positive (similar) and negative (dissimilar) samples. This is typically achieved by maintaining a queue of negative samples during training. Prior works in the area typically uses a fixed-length negative sample queue, but how the negative sample size affects the model performance remains unclear. The opaque impact of the number of negative samples on performance when employing contrastive learning aroused our in-depth exploration. This paper presents a momentum contrastive learning model with negative sample queue for sentence embedding, namely MoCoSE. We add the prediction layer to the online branch to make the model asymmetric and together with EMA update mechanism of the target branch to prevent the model from collapsing. We define a maximum traceable distance metric, through which we learn to what extent the text contrastive learning benefits from the historical information of negative samples. Our experiments find that the best results are obtained when the maximum traceable distance is at a certain range, demonstrating that there is an optimal range of historical information for a negative sample queue. We evaluate the proposed unsupervised MoCoSE on the semantic text similarity (STS) task and obtain an average Spearman’s correlation of 77.27%. Source code is available here.