Fig. 1. Identifying mutated protein assemblies as biomarkers of ICI response.

(A) Immunotherapy-treated patients are analyzed by computing somatic mutation burdens across a hierarchy of known and putative physical assemblies of proteins. Counts (n) refer to the number of patients in the Samstein discovery cohort (see text). This analysis reveals a constellation of protein assemblies for which the assembly-level mutation burden (AMB) is predictive of treatment outcomes. (B) The predictive power of the AMB profile is assessed using survival data in two independent validation cohorts. In addition, the AMB-derived risk score is compared to immunogenic phenotypes from tumor histopathology imaging and mRNA expression levels of tumor biopsies (middle), then further validated by CRISPR screens in mice (right).