Fig. 4: Overview of methylation analysis.
From: Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals
Ai Scores quantifying imbalances in the methylation burden in any of 377 regions (extracted from TCGA; see ‘Methods’) in each cancer plasma sample compared to the non-cancer plasma CBS controls. Each circle corresponds to a different region and red circles indicate over-methylation of the corresponding regions between the cancer plasma and the CBS controls. Aii Integrated methylation scores over all regions in each plasma sample. A red circle indicates an over-methylated plasma sample, when compared to the CBS controls. We identified correctly 28 out of 61 cancer plasma samples, which corresponds to a 45.9% sensitivity. B Integrated methylation scores against cancer stage and type (Bi) and monotonic increase of median integrated methylation scores with cancer stage (Bii). C In silico validation of methylation analysis at increasing ctDNA fractions. At each ctDNA fraction, we simulated 1000 non-cancer 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 87% at ctDNA fractions 0.9%. 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.
