Cell-Type Prototype-Informed Neural Network for Gene Expression Estimation from Pathology Images

Estimating slide- and patch-level gene expression profiles from pathology images enables rapid and low-cost molecular analysis with broad clinical impact. Despite strong results, existing approaches treat gene expression as a mere slide- or spot-level signal and do not incorporate the fact that the measured expression arises from the aggregation of underlying cell-level expression. To explicitly introduce this missing cell-resolved guidance, we propose a Cell-type Prototype-informed Neural Network (CPNN) that leverages publicly available single-cell RNA-sequencing datasets. Since single-cell measurements are noisy and not paired with histology images, we first estimate cell-type prototypes-mean expression profiles that reflect stable gene-gene co-variation patterns.CPNN then learns cell-type compositional weights directly from images and models the relationship between prototypes and observed bulk or spatial expression, providing a biologically grounded and structurally regularized prediction framework. We evaluate CPNN on three slide-level datasets and three patch-level spatial transcriptomics datasets. Across all settings, CPNN achieves the highest performance in terms of Spearman correlation. Moreover, by visualizing the inferred compositional weights, our framework provides interpretable insights into which cell types drive the predicted expression. Code is publicly available at https://github.com/naivete5656/CPNN.

Towards Spatial Transcriptomics-guided Pathological Image Recognition with Batch-Agnostic Encoder

Spatial transcriptomics (ST) is a novel technique that simultaneously captures pathological images and gene expression profiling with spatial coordinates. Since ST is closely related to pathological features such as disease subtypes, it may be valuable to augment image representation with pathological information. However, there are no attempts to leverage ST for image recognition ({\it i.e,} patch-level classification of subtypes of pathological image.). One of the big challenges is significant batch effects in spatial transcriptomics that make it difficult to extract pathological features of images from ST. In this paper, we propose a batch-agnostic contrastive learning framework that can extract consistent signals from gene expression of ST in multiple patients. To extract consistent signals from ST, we utilize the batch-agnostic gene encoder that is trained in a variational inference manner. Experiments demonstrated the effectiveness of our framework on a publicly available dataset. Code is publicly available at https://github.com/naivete5656/TPIRBAE