Fig. 4

Enhanced sensitivity of somatic genomic alterations detection in PDAC organoids compared to tumor samples. WES data was used to explore the genomic landscape of PDAC, revealing organoid cultures’ enhanced sensitivity in capturing the mutational landscape compared to tumor samples. (A) Number of small somatic mutations, including single nucleotide variants (SNVs), small insertions/deletions (InDels), and multi-nucleotide variants (MNVs) detected in the exome region for each sample. The y-axis is depicted logarithmically, and sample types (T for tumor, O for organoid) are indicated on the top. (B) Boxplot comparing the distribution of small somatic mutations between tumor tissues (dark green) and organoid samples (yellow), corresponding to the data in panel (A). (C) Number of small somatic mutations per megabase over the targeted exome region (tumor mutational burden, TMB). (D) Boxplot comparing TMB between tumor and organoid samples, based on (C). (E) Number of small somatic mutations leading to amino acid changes (Pr-coding). (F) Boxplot comparing Pr-coding mutations between tumor and organoid samples, based on (E). (G) In-silico estimated ploidy for each sample. (H) Boxplot comparing ploidy between tumor and organoid samples, based on (G). (I) In-silico estimated tumor purity. (J) Boxplot comparing tumor purity between groups, based on (I). (K) Number of copy number alteration (CNA) segments (CNA burden). Patient IDs are shown at the bottom. (L) Boxplot comparing CNA burden between tumor and organoid samples, based on (K). (M) Summary of neoadjuvant treatments administered. Median values for both groups are displayed next to the boxplots. P-values for all boxplots are calculated using the paired Wilcoxon test.