Figure 2. Dual Antigen Use Greatly Improves the Precision of Cancer Detection.

Antigen combinations were ranked by their clustering scores for each tumor and each gate type (e.g., clinical, novel, clinical-clinical, clinical-novel, or novelnovel). In this figure different subsets of the top antigens (e.g., the top scoring singlet/pair or the top 10 combinations) are taken and their F₁ scores are used to describe their potential discriminatory power.

(A) Distribution of tumor-versus-normal discrimination scores (F₁) for the top clinical antigens or top 10 novel antigens for each cancer type, and for the top 10 antigen pairs (clinical-clinical, clinical-novel, or novel-novel) for each cancer type. F₁ scores range between 0 (no sensitivity and specificity) and 1 (perfect precision and recall). Here, we see significant gains in discrimination power going from a clinical antigen to a single novel antigen (p = 8.41 × 10⁻⁶⁹; n = 646) and from a clinical-clinical antigen pair to a clinical-novel pair (p = 1,38 × 10⁻¹¹; n = 660).

(B) Improvement in tumor-versus-normal discrimination with dual antigen recognition by cancer type. F₁ scores are shown for the highest clustering score single clinical antigen and the highest clustering score dual antigen pair. All antigen pairs improve over the highest performing single clinical antigen.

(C) Pie chart showing the composition of different gate types of pairs in the top 10 per tumor type. A AND B gates have high expression of both antigens, A AND NOT B have high expression of one antigen and low expression of the second antigen. The majority of pairs are AND NOT gates.

(D) Novel antigens (hubs, blue) identified that form high-performing pairs with numerous current clinically targeted CAR antigens (spokes, orange). Edge weights and color correspond to the number of applicable cancer types.