Can Protein-Derived Knowledge Improve Pathology Foundation Models?

Di Zhang, Zhangpeng Gong, Jiashuai Liu, Zhi Zeng, Jiusong Ge +8

Molecularly guided pathology foundation models (PFMs) exploit transcriptomic or proteomic information to enrich whole-slide image (WSI) representations, yet effectively leveraging large standalone molecular corpora remains challenging. First, existing molecular foundation models encode protein sequences or single-cell states, not the patient-level bulk expression profiles paired with WSIs. Second, because cross-modal supervision is restricted to paired WSI-omics samples, knowledge from standalone molecular corpora reaches the pathology encoder only indirectly, creating a paired-support bottleneck. To address these challenges, we propose a three-stage framework that decouples proteomic knowledge acquisition from cross-modal transfer, yielding ProSlide, a slide-level hierarchical pathology foundation model. First, to close the modality gap, we pretrain a Proteomic Foundation Encoder (PFE) on 12,695 sample-level bulk protein profiles using virtual profile generation and expression-space multi-view pretraining. Second, we pretrain ProSlide, a patch-region-slide encoder, to predict protein expression from paired WSI-protein samples. Third, to relax the paired-support bottleneck, we…