《Bioinformatics》Autoencoder-based drug–target interaction prediction by preserving the consistency of chemical properties and functions of drugs
摘要:
探索潜在的药物-靶标相互作用(DTIs)是药物发现和药物重定位的关键步骤。计算预测可能存在相互作用的药物-靶标对可以有效的减少生物湿实验的工作量。但是,大多数之前的研究没有考虑到药物的化学性质(化学指纹)和功能(靶向蛋白)间的一致性,这一关系的变化可能会对DTI的预测造成严重的负面影响。
该文章提出了一种基于自动编码器的方法(AEFS),通过保持药物相关性在化学属性空间、分子机制空间和临床功能空间中的分布相一致来预测药物的可能靶点。实验表明,AEFS具有强大的发现未知DTI的能力,并且它对不平衡的数据的鲁棒性更强。其性能在多个评价指标下都显著的优于几个SOTA方法。
Abstract:
Exploring the potential drug-target interactions (DTIs) is a key step in drug discovery and repurposing. In recent years, predicting the probable DTIs through computational methods has gradually become a research hot spot. However, most of the previous studies failed to judiciously take into account the consistency between the chemical properties of drug and its functions. The changes of these relationships may lead to a severely negative effect on the prediction of DTIs.
We propose an autoencoder-based method, AEFS, under spatial consistency constraints to predict DTIs. A heterogeneous network is established to integrate the information of drugs, proteins and diseases. The original drug features are projected to an embedding (protein) space by a multi-layer encoder, and further projected into label (disease) space by a decoder. In this process, the clinical information of drugs is introduced to assist the DTI prediction. By maintaining the distribution of drug correlation in the original feature, embedding and label space, AEFS keeps the consistency between chemical properties and functions of drugs. Experimental comparisons indicate that AEFS is more robust for imbalanced data and of significantly superior performance in DTI prediction. Case studies further confirm its ability to mine the latent drug-target interactions.
文章链接:https://academic.oup.com/bioinformatics/article/37/20/3618/6279744
代码地址:https://github.com/JackieSun818/AEFS
根据药物的化学指纹、靶点、适应症,我们分别计算了药物在药物空间、靶标空间、疾病空间中的相似性。如图2所示,药物在不同空间中的相似性的差异较大,这可能是由于药物的靶蛋白数据与适应症数据存在一定程度的特征缺失。因此,我们尝试在预测的过程中,保持药物间的相似性在三个空间中的一致性,以提升预测算法的准确性。
试验结果(图3、图4)表明,AEFS在AUC、AUPR、Recall等多个评价指标上,均优于几个SOTA算法。
[1] Sun C , Cao Y , Wei J M , et al. Autoencoder-based Drug-Target Interaction Prediction by Preserving the Consistency of Chemical Properties and Functions of Drugs[J]. Bioinformatics, 2021.