It is clinically crucial and potentially very beneficial to be able to analyze and model directly the spatial distributions of cells in histopathology whole slide images (WSI). However, most existing WSI datasets lack cell-level annotations, owing to the extremely high cost over giga-pixel images. Thus, it remains an open question whether deep learning models can directly and effectively analyze WSIs from the semantic aspect of cell distributions. In this work, we construct a large-scale WSI dataset with more than 5 billion cell-level annotations, termed WSI-Cell5B, and a novel hierarchical Cell Cloud Transformer (CCFormer) to tackle these challenges. WSI-Cell5B is based on 6,998 WSIs of 11 cancers from The Cancer Genome Atlas Program, and all WSIs are annotated per cell by coordinates and types. To the best of our knowledge, WSI-Cell5B is the first WSI-level large-scale dataset integrating cell-level annotations. On the other hand, CCFormer formulates the collection of cells in each WSI as a cell cloud and models cell spatial distribution. Specifically, Neighboring Information Embedding (NIE) is proposed to characterize the distribution of cells within the neighborhood of each cell, and a novel Hierarchical Spatial Perception (HSP) module is proposed to learn the spatial relationship among cells in a bottom-up manner. The clinical analysis indicates that WSI-Cell5B can be used to design clinical evaluation metrics based on counting cells that effectively assess the survival risk of patients. Extensive experiments on survival prediction and cancer staging show that learning from cell spatial distribution alone can already achieve state-of-the-art (SOTA) performance, i.e., CCFormer strongly outperforms other competing methods.

Learning with noisy labels (LNL) poses a significant challenge in training a well-generalized model while avoiding overfitting to corrupted labels. Recent advances have achieved impressive performance by identifying clean labels and correcting corrupted labels for training. However, the current approaches rely heavily on the model's predictions and evaluate each sample independently without considering either the global and local structure of the sample distribution. These limitations typically result in a suboptimal solution for the identification and correction processes, which eventually leads to models overfitting to incorrect labels. In this paper, we propose a novel optimal transport (OT) formulation, called Curriculum and Structure-aware Optimal Transport (CSOT). CSOT concurrently considers the inter- and intra-distribution structure of the samples to construct a robust denoising and relabeling allocator. During the training process, the allocator incrementally assigns reliable labels to a fraction of the samples with the highest confidence. These labels have both global discriminability and local coherence. Notably, CSOT is a new OT formulation with a nonconvex objective function and curriculum constraints, so it is not directly compatible with classical OT solvers. Here, we develop a lightspeed computational method that involves a scaling iteration within a generalized conditional gradient framework to solve CSOT efficiently. Extensive experiments demonstrate the superiority of our method over the current state-of-the-arts in LNL. Code is available at https://github.com/changwxx/CSOT-for-LNL.