arXiv:2510.14419cs.LGstat.ML2025-10被引 1

提出新评估指标,精准衡量药物靶点相互作用方向预测能力。

Interaction Concordance Index: Performance Evaluation for Interaction Prediction Methods

  • 引入交互一致性指数(IC-index),评估预测方向正确率
  • 实验证明现有模型在未见实体时方向预测失效
  • 适合医药研发中需精准匹配药物与靶点的场景

给定两组实体及其相互亲和值(如药物-靶点亲和力,DTA),若药物对某一靶点的作用依赖于该靶点,则认为存在相互作用。交互存在意味着将药物分配给靶点与反向分配所得整体亲和力不同。准确捕捉交互关系有助于优化有限药物剂量的最优靶点匹配。当前预测方法通常仅基于已知亲和力或结合化学结构等辅助信息。本文提出交互方向预测性能评估指标——交互一致性指数(IC-index),适用于固定预测器及机器学习算法。该指标通过评估数据中交互方向预测正确的比例,补充了传统亲和力预测评估方法。首先证明了当预测器无法捕捉交互时,IC-index保持不变;其次表明,若学习算法对药物和靶点身份具有置换等变性,则在训练中未见过的药物或靶点情况下无法识别交互。实际应用中可通过引入合适的辅助信息(如分子结构)解决此问题。我们在多个生物医学交互数据集上对多种先进机器学习算法进行了全面实验,结果揭示了不同类型亲和力预测方法在IC-index上的表现差异,为现有评估体系提供了重要补充。

原文摘要 · Abstract (English)

Consider two sets of entities and their members' mutual affinity values, say drug-target affinities (DTA). Drugs and targets are said to interact in their effects on DTAs if drug's effect on it depends on the target. Presence of interaction implies that assigning a drug to a target and another drug to another target does not provide the same aggregate DTA as the reversed assignment would provide. Accordingly, correctly capturing interactions enables better decision-making, for example, in allocation of limited numbers of drug doses to their best matching targets. Learning to predict DTAs is popularly done from either solely from known DTAs or together with side information on the entities, such as chemical structures of drugs and targets. In this paper, we introduce interaction directions' prediction performance estimator we call interaction concordance index (IC-index), for both fixed predictors and machine learning algorithms aimed for inferring them. IC-index complements the popularly used DTA prediction performance estimators by evaluating the ratio of correctly predicted directions of interaction effects in data. First, we show the invariance of IC-index on predictors unable to capture interactions. Secondly, we show that learning algorithm's permutation equivariance regarding drug and target identities implies its inability to capture interactions when either drug, target or both are unseen during training. In practical applications, this equivariance is remedied via incorporation of appropriate side information on drugs and targets. We make a comprehensive empirical evaluation over several biomedical interaction data sets with various state-of-the-art machine learning algorithms. The experiments demonstrate how different types of affinity strength prediction methods perform in terms of IC-index complementing existing prediction performance estimators.

药物靶点交互预测评估指标

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