Keunho Byeon

Keunho Byeon, Sunhong Park, Jeewoo Lim et al.

Spatial transcriptomics enables profiling of spatial gene expression but is limited by high cost and low throughput, motivating prediction from H&E histopathology images. Existing context-aware methods mainly supervise absolute expression, while relative expression relationships between spots are rarely used explicitly. We propose COAST, a context-aware differential learning framework for spatial gene expression prediction. COAST conditions the local and global context features with type-specific modulation and aggregates the target and context spot tokens using a Transformer encoder to capture both fine-grained local patterns and slide-level structure. It is trained with a joint objective that combines absolute expression regression with signed differential regression between the target and context spots. Experiments on multiple spatial transcriptomics datasets show consistent improvements in correlation- and distribution-based metrics, demonstrating the effectiveness of context-aware differential learning for histology-based spatial gene expression prediction.

Jaeung Lee, Keunho Byeon, Jin Tae Kwak

Cancer grading is an essential task in pathology. The recent developments of artificial neural networks in computational pathology have shown that these methods hold great potential for improving the accuracy and quality of cancer diagnosis. However, the issues with the robustness and reliability of such methods have not been fully resolved yet. Herein, we propose a centroid-aware feature recalibration network that can conduct cancer grading in an accurate and robust manner. The proposed network maps an input pathology image into an embedding space and adjusts it by using centroids embedding vectors of different cancer grades via attention mechanism. Equipped with the recalibrated embedding vector, the proposed network classifiers the input pathology image into a pertinent class label, i.e., cancer grade. We evaluate the proposed network using colorectal cancer datasets that were collected under different environments. The experimental results confirm that the proposed network is able to conduct cancer grading in pathology images with high accuracy regardless of the environmental changes in the datasets.

Keunho Byeon, Jin Tae Kwak

Spatial transcriptomics offers spatially resolved gene expression profiling within tissue sections, but its cost and limited throughput hinder large-scale deployment. To extend this capability to routine practice, recent computational methods aim to infer spatial gene expression directly from ubiquitous hematoxylin and eosin-stained histology slides. However, most existing models assume Cartesian or geometry-agnostic locality, despite the hexagonal sampling of widely used spot-array platforms, and point-wise regression objectives often yield over-smoothed gene expression profiles, obscuring gene-specific spatial heterogeneity. To address these, we propose HEXST, a geometry-aligned Transformer for spatial gene expression prediction from histology. HEXST operates directly on hexagonal spot coordinates to enable efficient local-to-global contextual modeling via tailored shifted-window attention mechanism and hexagonal rotary positional encoding. To enhance gene-wise spatial contrast, HEXST complements point-wise regression with a contrast-sensitive differential objective and transcriptomic priors from a pretrained single-cell foundation model during training. Across seven spatial transcriptomics datasets, HEXST consistently outperforms state-of-the-art models, providing accurate and robust spatial gene expression predictions while preserving gene-wise contrast and spatial heterogeneity.

Ju Cheon Lee, Keunho Byeon, Boram Song et al.

In computational pathology, cancer grading has been mainly studied as a categorical classification problem, which does not utilize the ordering nature of cancer grades such as the higher the grade is, the worse the cancer is. To incorporate the ordering relationship among cancer grades, we introduce a differential ordinal learning problem in which we define and learn the degree of difference in the categorical class labels between pairs of samples by using their differences in the feature space. To this end, we propose a transformer-based neural network that simultaneously conducts both categorical classification and differential ordinal classification for cancer grading. We also propose a tailored loss function for differential ordinal learning. Evaluating the proposed method on three different types of cancer datasets, we demonstrate that the adoption of differential ordinal learning can improve the accuracy and reliability of cancer grading, outperforming conventional cancer grading approaches. The proposed approach should be applicable to other diseases and problems as they involve ordinal relationship among class labels.

Jeaung Lee, Jeewoo Lim, Keunho Byeon et al.

In computational pathology, several foundation models have recently emerged and demonstrated enhanced learning capability for analyzing pathology images. However, adapting these models to various downstream tasks remains challenging, particularly when faced with datasets from different sources and acquisition conditions, as well as limited data availability. In this study, we benchmark four pathology-specific foundation models across 14 datasets and two scenarios-consistency assessment and flexibility assessment-addressing diverse adaptation scenarios and downstream tasks. In the consistency assessment scenario, involving five fine-tuning methods, we found that the parameter-efficient fine-tuning approach was both efficient and effective for adapting pathology-specific foundation models to diverse datasets within the same downstream task. In the flexibility assessment scenario under data-limited environments, utilizing five few-shot learning methods, we observed that the foundation models benefited more from the few-shot learning methods that involve modification during the testing phase only. These findings provide insights that could guide the deployment of pathology-specific foundation models in real clinical settings, potentially improving the accuracy and reliability of pathology image analysis. The code for this study is available at: https://github.com/QuIIL/BenchmarkingPathologyFoundationModels.

Jiamu Wang, Keunho Byeon, Jinsol Song et al.

Anomaly detection is an emerging approach in digital pathology for its ability to efficiently and effectively utilize data for disease diagnosis. While supervised learning approaches deliver high accuracy, they rely on extensively annotated datasets, suffering from data scarcity in digital pathology. Unsupervised anomaly detection, however, offers a viable alternative by identifying deviations from normal tissue distributions without requiring exhaustive annotations. Recently, denoising diffusion probabilistic models have gained popularity in unsupervised anomaly detection, achieving promising performance in both natural and medical imaging datasets. Building on this, we incorporate a vision-language model with a diffusion model for unsupervised anomaly detection in digital pathology, utilizing histopathology prompts during reconstruction. Our approach employs a set of pathology-related keywords associated with normal tissues to guide the reconstruction process, facilitating the differentiation between normal and abnormal tissues. To evaluate the effectiveness of the proposed method, we conduct experiments on a gastric lymph node dataset from a local hospital and assess its generalization ability under domain shift using a public breast lymph node dataset. The experimental results highlight the potential of the proposed method for unsupervised anomaly detection across various organs in digital pathology. Code: https://github.com/QuIIL/AnoPILaD.