Fig. 5: Integration of genomic data modalities for ctDNA detection.
From: Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals
A Multimodal scores for the quantification of plasma ctDNA generated from the integration of copy number aberrations, somatic SNVs and INDELs, and methylation signals in each plasma sample. A red circle indicates a higher ctDNA burden in comparison to the non-cancer CBS controls. 52 out of 61 cancer plasma samples were correctly identified as such, which corresponds to 85.2% sensitivity. This is higher than the sensitivity of any of the three data modalities. B Multimodal scores against cancer stage and type (Bi) and monotonic increase of median multimodal scores with cancer stage (Bii). C In silico validation of multimodal analysis at increasing ctDNA fractions. At each ctDNA fraction, we simulated 1000 controls and 1000 cancer plasma samples using actual non-cancer and cancer plasma samples as templates (see Methods). The area under the receiver operating characteristic (ROC) curve (AUC) is 86% at ctDNA fractions 0.7%. CTRL CBS controls (n = 9 subjects), CRC colorectal (n = 36 subjects), OES oesophageal (n = 8 subjects), PNCR pancreatic (n = 6 subjects), RNL renal (n = 5 subjects), OVR ovarian (n = 4 subjects), BST breast (n = 2 subjects). For each boxplot in (Bi, C), the box bounds, and centre correspond to the 25th, 50th (median) and 75th percentiles of the data in each corresponding group, and the whiskers extend to 1.5 times the interquartile range (IQR) above and below the box bounds. Source data is provided as a source data file.
