CellPlex: Benchmarking Single-Cell Spatial Proteomics Prediction from H&E

Zijun Gao, Yijiang Chen, Xiangde Luo, Pheng-Ann Heng

Spatial proteomics measures tens of proteins in every cell of a tissue section, but its cost confines it to small research cohorts, whereas hematoxylin and eosin (H\&E) slides exist for nearly every patient. Inferring single-cell spatial proteomics from H\&E would bring its analyses to routine pathology, and a growing number of virtual staining models pursue this goal. Each is evaluated on its own cohort, panel and pixel-level metric, and released models transfer poorly to new cohorts, leaving open which approach to build on and which proteins H\&E can reveal. We introduce CellPlex, a benchmark that poses the task at the level of the cell: seven cohorts with same-section H\&E and multiplexed immunofluorescence, from colorectal and breast cancer to lymph-node metastases, bone marrow and glioma, with 717 samples, 44.8 million cells and 149 proteins, processed by one pipeline into per-cell targets. Pathology foundation models (PFMs) are adapted with one cell-level protocol, specialist models are fine-tuned under a matched budget, and all are scored on the same cells. Adapted PFMs are the most accurate models on every cohort, ahead of the specialists even after fine-tuning, but keep…