Schistosomiasis is a tropical disease that poses a significant risk to hundreds of millions of people, yet often goes unnoticed. While praziquantel, a widely used anti-schistosome drug, has a low cost and a high cure rate, it has several drawbacks. These include ineffectiveness against schistosome larvae, reduced efficacy in young children, and emerging drug resistance. Discovering new and active anti-schistosome small molecules is therefore critical, but this process presents the challenge of low accuracy in computer-aided methods. To address this issue, we proposed GNN-DDAS, a novel deep learning framework based on graph neural networks (GNN), designed for drug discovery to identify active anti-schistosome (DDAS) small molecules. Initially, a multi-layer perceptron was used to derive sequence features from various representations of small molecule SMILES. Next, GNN was employed to extract structural features from molecular graphs. Finally, the extracted sequence and structural features were then concatenated and fed into a fully connected network to predict active anti-schistosome small molecules. Experimental results showed that GNN-DDAS exhibited superior performance compared to the benchmark methods on both benchmark and real-world application datasets. Additionally, the use of GNNExplainer model allowed us to analyze the key substructure features of small molecules, providing insight into the effectiveness of GNN-DDAS. Overall, GNN-DDAS provided a promising solution for discovering new and active anti-schistosome small molecules.

中文翻译：

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GNN-DDAS：基于图神经网络的抗血吸虫小分子鉴定药物发现


血吸虫病是一种热带病，对数亿人构成重大风险，但往往被忽视。虽然吡喹酮是一种广泛使用的抗血吸虫药物，成本低，治愈率高，但它也有几个缺点。这些因素包括对血吸虫幼虫无效、对幼儿疗效降低以及新出现的耐药性。因此，发现新的和活跃的抗血吸小分子至关重要，但这个过程在计算机辅助方法中提出了准确性低的挑战。为了解决这个问题，我们提出了 GNN-DDAS，这是一种基于图神经网络 （GNN） 的新型深度学习框架，旨在用于药物发现以识别活性抗血吸虫 （DDAS） 小分子。最初，多层感知器用于从小分子 SMILES 的各种表示中推导出序列特征。接下来，采用 GNN 从分子图中提取结构特征。最后，将提取的序列和结构特征连接起来，并输入到一个全连接网络中，以预测活性抗血吸小分子。实验结果表明，与基准方法相比，GNN-DDAS 在基准和真实世界应用程序数据集上都表现出优异的性能。此外，GNNExplainer 模型的使用使我们能够分析小分子的关键子结构特征，从而深入了解 GNN-DDAS 的有效性。总体而言，GNN-DDAS 为发现新的活性抗血吸虫小分子提供了一个有前途的解决方案。