提出双分支框架,提升药物活性悬崖预测的准确性与稳定性。
CliffRank: A Dual-Branch Framework for Activity-Cliff Ranking Prediction
- 结合绝对活性回归与排序一致性学习,双分支并行训练。
- 在三组肽类数据上达0.5393的Spearman相关性,小分子数据上0.6890。
- 引入偏好一致性机制,适合药物研发与活性预测场景。
活性悬崖预测仍具挑战,因局部结构变化可引发显著活性差异,且高质量数据有限。为更有效利用现有活性标签,本文结合绝对活性回归与排序一致性学习。CliffRank采用双分支结构,通过均方误差、阈值化列表损失及成对偏好一致性(PPC)进行训练,使偏好概率空间中的相对顺序保持一致。在三个抗菌肽数据集上,使用ESM2-t12的CliffRank达到最高均值Spearman相关系数0.5393和均值Recall@50 21.4,尽管领先方法在不同数据集间有所变化。在三个小分子数据集上,采用PNA模型且在120轮后激活PPC时,均值Spearman相关系数达0.6890,均值Recall@50为30.4,与ACANet-PNA持平。PPC效果也揭示了其实际应用边界。不对称初始化提升了MolCLR-GIN平均表现,但未对所有目标均有效。对于无预训练权重的PNA,延迟触发PPC改善部分指标,但无统一调度方案能同时优化相关系数与召回率。未来工作应评估更多靶点与抗菌肽体系,开发自适应PPC调度策略,并在有蛋白或膜环境信息时加以整合。
原文摘要 · Abstract (English)
Activity-cliff ranking remains difficult because local structural changes can cause large activity differences, while high-quality data that resolve the underlying mechanisms remain limited. To use available activity labels more effectively, we combine absolute-activity regression with ranking-consistency learning. CliffRank trains two parallel predictors with mean squared error, a thresholded listwise loss, and Pairwise Preference Consistency (PPC), which aligns relative ordering in the preference-probability space. On three antimicrobial peptide datasets, CliffRank with ESM2-t12 achieved the highest mean Spearman correlation of 0.5393 and mean Recall@50 of 21.4, although the leading method varied across individual datasets. On three small-molecule datasets, CliffRank with PNA, where PPC was activated after 120 epochs, achieved the highest mean Spearman correlation of 0.6890, while its mean Recall@50 of 30.4 matched that of ACANet-PNA. The PPC results also define its practical limits. Asymmetric initialization improved the MolCLR-GIN averages but did not improve every target. For PNA without pretrained weights, delayed PPC improved selected metrics, but no schedule was best for both mean Spearman correlation and mean Recall@50. Future work should evaluate more targets and antimicrobial peptide systems, develop adaptive PPC schedules, and incorporate protein or membrane context when available.
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