提出预算约束的关联多实例学习框架,高效预测miRNA靶点。
PAIR-Former: Budgeted Relational Multi-Instance Learning for Functional miRNA Target Prediction
- 通过设置计算预算K,仅对精选的少数候选位点进行深度关联分析。
- 在多个数据集上达到F1=0.840,远超现有方法,且在42万对数据上仍有效。
- 适用于高规模生物序列分析,也推广至医学图像等其他领域。
功能性miRNA-mRNA靶向预测是一个大规模分组问题,每个转录本产生大量候选靶点(CTSs),但仅能获得成对标签。以往方法使用最大池化处理单个候选评分,忽略了位点间的关联模式,而这些模式对准确预测至关重要。然而,直接建模这些关系的计算成本高达$/mathcal{O}(n^2)$,当$ n $达数千时不可行;仅简单扫描又会丢失关键相互作用。为此,本文提出 extit{预算约束的关联多实例学习}(BR-MIL),将计算预算$ K $作为核心约束,即每组最多仅对$ K $个实例进行昂贵编码与关系处理。理论证明,近似质量与泛化能力由$ K $决定而非原始袋大小$ n $。基于此,提出 extbf{PAIR-Former}:先廉价扫描所有候选,选取$ K $个多样化位点,再用集合变换器聚合。实验显示,该方法在miRAW(10折平衡交叉验证)上取得F1=0.840,deepTargetPro上为0.839,在大规模MTI基准(42万对,$38\times$更大)上达0.793,证明其在海量数据下仍可扩展,优于传统方法。额外在CAMELYON16和Musk2上的结果表明,该框架亦适用于非生物序列任务。
原文摘要 · Abstract (English)
Functional miRNA--mRNA targeting is a large-bag prediction problem where each transcript yields a heavy-tailed pool of candidate target sites (CTSs), yet only a pair-level label is observed. Prior methods use max-pooling over individual CTS scores, ignoring relational patterns among sites, but modeling these patterns is critical for accuracy. The challenge is that naive relational aggregation incurs $\mathcal{O}(n^2)$ cost, prohibitive when $n$ reaches thousands, yet a cheap scan alone discards the very interactions that drive functional repression. We formalize this tension as \emph{Budgeted Relational Multi-Instance Learning (BR-MIL)}, a new MIL problem where the compute budget $K$ is a first-class constraint such that at most $K$ instances per bag may receive expensive encoding and relational processing. We establish theoretical foundations for BR-MIL, proving that both approximation quality and generalization are governed by $K$ rather than the raw bag size $n$. Building on this theory, we propose \textbf{PAIR-Former}, which scans all candidates cheaply, selects $K$ diverse CTSs, and aggregates them via Set Transformer. PAIR-Former achieves state-of-the-art performance, outperforming all reproduced baselines with F1$=0.840$ on miRAW (10-fold balanced CV) and $0.839$ on deepTargetPro in transfer evaluation, while achieving $0.793$ on the large-scale MTI benchmark (420K pairs, $38\times$ larger), demonstrating that budgeted relational MIL scales where naive approaches fail. Additional results on CAMELYON16 and Musk2 further show that the proposed BR-MIL formulation extends beyond biological sequence modeling.
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