使用多种人工智能算法预测化合物-靶点相互作用并与基于共识的策略进行比较。

Prediction of compound-target interaction using several artificial intelligence algorithms and comparison with a consensus-based strategy.

作者信息

Jimenes-Vargas Karina, Pazos Alejandro, Munteanu Cristian R, Perez-Castillo Yunierkis, Tejera Eduardo

机构信息

Bio-Cheminformatics Research Group, Universidad de Las Américas, Quito, 170504, Ecuador.

Departament of Computer Science and Information Technologies, Faculty of Computer Science, Universidade da Coruña, Campus Elviña s/n, 15071, A Coruña, Spain.

出版信息

J Cheminform. 2024 Mar 7;16(1):27. doi: 10.1186/s13321-024-00816-1.

Abstract

For understanding a chemical compound's mechanism of action and its side effects, as well as for drug discovery, it is crucial to predict its possible protein targets. This study examines 15 developed target-centric models (TCM) employing different molecular descriptions and machine learning algorithms. They were contrasted with 17 third-party models implemented as web tools (WTCM). In both sets of models, consensus strategies were implemented as potential improvement over individual predictions. The findings indicate that TCM reach f1-score values greater than 0.8. Comparing both approaches, the best TCM achieves values of 0.75, 0.61, 0.25 and 0.38 for true positive/negative rates (TPR, TNR) and false negative/positive rates (FNR, FPR); outperforming the best WTCM. Moreover, the consensus strategy proves to have the most relevant results in the top of target profiles. TCM consensus reach TPR and FNR values of 0.98 and 0; while on WTCM reach values of 0.75 and 0.24. The implemented computational tool with the TCM and their consensus strategy at: https://bioquimio.udla.edu.ec/tidentification01/ . Scientific Contribution: We compare and discuss the performances of 17 public compound-target interaction prediction models and 15 new constructions. We also explore a compound-target interaction prioritization strategy using a consensus approach, and we analyzed the challenging involved in interactions modeling.

摘要

为了理解化合物的作用机制及其副作用,以及进行药物发现,预测其可能的蛋白质靶点至关重要。本研究考察了15个采用不同分子描述和机器学习算法开发的以靶点为中心的模型(TCM)。它们与17个作为网络工具实现的第三方模型(WTCM)进行了对比。在这两组模型中,都实施了共识策略,作为对个体预测的潜在改进。研究结果表明,TCM的F1分数值大于0.8。比较这两种方法,最佳的TCM在真阳性/阴性率(TPR、TNR)和假阴性/阳性率(FNR、FPR)方面分别达到了0.75、0.61、0.25和0.38的值;优于最佳的WTCM。此外,共识策略在靶点概况排名中被证明具有最相关的结果。TCM共识的TPR和FNR值分别为0.98和0;而WTCM的这两个值分别为0.75和0.24。带有TCM及其共识策略的计算工具可在以下网址获取:https://bioquimio.udla.edu.ec/tidentification01/ 。科学贡献:我们比较并讨论了17个公共化合物-靶点相互作用预测模型和15个新构建模型的性能。我们还探索了一种使用共识方法的化合物-靶点相互作用优先级策略,并分析了相互作用建模中涉及的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a39/10919000/9d24af9808e1/13321_2024_816_Fig1_HTML.jpg

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