Statistical Testing for Multiple Instance Learning via Selective Inference with Applications to Computational Pathology

Noriaki Hashimoto, Shuichi Nishino, Teruyuki Katsuoka, Tomohiro Shiraishi, Daiki Miwa +5

Multiple instance learning (MIL) is widely used in computational pathology because it enables weakly supervised analysis of whole-slide images (WSIs) without requiring patch-level annotations. In attention-based MIL, instances with high attention scores are often interpreted as diagnostically important regions and used as visual explanations. However, attention scores alone cannot determine whether selected high-attention instances are significantly different from normal instances, limiting the reliability of attention-based explanations. In this paper, we formulate the evaluation of high-attention instances as a statistical hypothesis testing problem. Specifically, we assess whether a selected high-attention instance significantly deviates from a representative normal reference instance selected based on feature similarity. A major challenge is that both the target instance and the reference instance are selected through data-dependent procedures, rendering standard hypothesis testing invalid. To address this issue, we introduce a selective inference (SI) framework that explicitly accounts for the selection events induced by attention-based instance selection and adaptive…