Fig. 2

The Workflow of Data Analysis, the Distribution of the Top Ten Volatile Organic Compound (VOC) Ions with High Contribution Coefficients in the Models Construction, and the Performance of the Breast Cancer Detection Models for the BreathBC Model and BreathBC-Plus Model. A The workflow of data analysis and models construction. Breath samples were collected through standardized breath collection procedures using self-designed collectors and airbags and then analyzed by the high-pressure photon ionization–time-of-flight mass spectrometry (HPPI-TOFMS). Data for 1500 VOC ions were detected from the m/z range of [20, 320) with an interval of 0.2. Based on the random forest algorithm, the optimal 10 VOC ions were confirmed based on the feature importance or coefficient in the model training. Two breast cancer detection models (BreathBC and BreathBC-Plus) were constructed using the breath VOC markers with or without risk factors. Both models were verified with the three external validation cohorts. B Ten optimal VOC ions demonstrated significant differences between patients with breast cancer and non-cancer women among all the participants in this study, including eight elevated VOCs and two decreased VOCs. C The receiver operating characteristic (ROC) curves and the associated areas under curves (AUCs) of the diagnostic performance of the ten optimal VOC ions. D–E For the BreathBC model using 10 breath VOC markers, the diagnostic AUC was 0.96 (95% CI, 0.94–0.97) in the internal validation cohort, 0.95 (95% CI, 0.93–0.90) in the test cohort (D), and 0.87 in the external validation cohorts (E). F, G For the BreathBC-Plus model using both breath VOC markers and risk factors, the combined model performed better than the BreathBC model in the internal validation cohort and the test cohort (AUC = 0.97–0.98) (F) and the external validation cohorts (AUC = 0.94) (G). Abbreviation: AUC, areas under curve. Abbreviation: HPPI-TOFMS, high-pressure photon ionization–time-of-flight mass spectrometry; VOC, volatile organic compound; BC, breast cancer; HC, healthy control; AUC, areas under curve