Jensen, C. B.; Sakhteman, A.; Hamood, F.; Schneider, A.; Woortman, J.; Teleanu, M.-V.; Horak, P.; Bayer, F. P.; Stange, C.; Huellein, J.; Hübschmann, D.; Henssen, A. G.; Fröhling, S.; Kuster, B.; The, M.

The molecular tumor board (MTB) is central to precision oncology, providing personalized treatment recommendations based on molecular profiles of patient tumors. Genomics is instrumental for MTBs but often fails to identify clinically actionable targets, a gap that phosphoproteomics can fill. We present the tumor proteome activity status (TOPAS) platform, an end to end analysis pipeline that converts terabytes of phosphoproteomic data into patient-specific reports for MTB discussions, focusing on clinically relevant signaling linked to oncogenic mechanisms and therapeutic targets. Designed to scale with growing cohorts, the platform integrates data from 1,998 tumor samples to support patient- and cohort-level hypothesis generation. A web portal handles quality control, calculates TOPAS scores, identifies tumor antigens and immune checkpoints, and offers interactive analyses of differential protein abundance and outlier detection. The TOPAS platform is open source, addresses a critical unmet need and facilitates broader adoption of phosphoproteomics in precision oncology in the future.