论文标题
SSM-DTA:打破药物目标亲和力预测中数据稀缺的障碍
SSM-DTA: Breaking the Barriers of Data Scarcity in Drug-Target Affinity Prediction
论文作者
论文摘要
准确预测药物目标亲和力(DTA)对于早期药物发现至关重要,促进可以有效地与特定靶标相互作用并调节其活性的药物的鉴定。尽管湿实验仍然是最可靠的方法,但它们是耗时且资源密集的,导致数据可用性有限,这对深度学习方法构成了挑战。现有方法主要集中于基于可用DTA数据开发技术,而无需充分解决数据稀缺问题。为了克服这一挑战,我们提出了SSM-DTA框架,该框架结合了三种简单但高效的策略:(1)一种多任务训练方法,将DTA预测与蒙版语言建模(MLM)结合使用,使用配对的药品 - taget数据结合使用。 (2)一种半监督的训练方法,该方法利用大规模的未配对分子和蛋白质来增强药物和靶标表示。这种方法与以前仅在预训练中使用分子或蛋白质的方法不同。 (3)将轻质跨意识模块的整合以改善药物与靶标之间的相互作用,从而进一步提高预测准确性。通过在BindingDB,Davis和Kiba等基准数据集上进行的广泛实验,我们证明了框架的出色性能。此外,我们对特定的药物目标结合活动,虚拟筛查实验,药物可视化和现实世界应用进行了案例研究,所有这些都展示了我们工作的重要潜力。总之,我们提出的SSM-DTA框架解决了DTA预测中的数据限制挑战,并产生了令人鼓舞的结果,为更有效,更准确的药物发现过程铺平了道路。我们的代码可在$ \ href {https://github.com/qizhipei/ssm-dta} {github} $中获得。
Accurate prediction of Drug-Target Affinity (DTA) is of vital importance in early-stage drug discovery, facilitating the identification of drugs that can effectively interact with specific targets and regulate their activities. While wet experiments remain the most reliable method, they are time-consuming and resource-intensive, resulting in limited data availability that poses challenges for deep learning approaches. Existing methods have primarily focused on developing techniques based on the available DTA data, without adequately addressing the data scarcity issue. To overcome this challenge, we present the SSM-DTA framework, which incorporates three simple yet highly effective strategies: (1) A multi-task training approach that combines DTA prediction with masked language modeling (MLM) using paired drug-target data. (2) A semi-supervised training method that leverages large-scale unpaired molecules and proteins to enhance drug and target representations. This approach differs from previous methods that only employed molecules or proteins in pre-training. (3) The integration of a lightweight cross-attention module to improve the interaction between drugs and targets, further enhancing prediction accuracy. Through extensive experiments on benchmark datasets such as BindingDB, DAVIS, and KIBA, we demonstrate the superior performance of our framework. Additionally, we conduct case studies on specific drug-target binding activities, virtual screening experiments, drug feature visualizations, and real-world applications, all of which showcase the significant potential of our work. In conclusion, our proposed SSM-DTA framework addresses the data limitation challenge in DTA prediction and yields promising results, paving the way for more efficient and accurate drug discovery processes. Our code is available at $\href{https://github.com/QizhiPei/SSM-DTA}{Github}$.