ProLM: a plasma proteomics pretrained model for the general population

Plasma proteomics can provide a dynamic molecular readout of human health, but models that learn generalizable protein-expression patterns in population cohorts remain limited. Here we show that ProLM, a BERT-based plasma proteomics model pretrained on 15,499 relatively healthy UK Biobank participants, captures baseline protein-expression relationships and supports prediction of 16 common chronic diseases. After disease-specific fine-tuning, the ProLM-derived proteomic risk score outperformed the Age+Sex model for all 16 diseases, the cardiovascular disease (ASCVD) risk equation for 14 diseases and a 35-variable clinical PANEL score for 11 diseases. Model interpretation highlighted proteins including GDF15 whose expression changed more than 15 years before clinical diagnosis, and key findings were externally evaluated in the China Kadoorie Biobank. These results support plasma proteomics pretrained models as tools for early chronic-disease risk stratification, while prospective validation is needed before clinical implementation. The authors show a plasma proteomics pretrained model that predicts chronic disease risk across population cohorts and highlights proteins with altered expression years before diagnosis.