Gastric cancer genomics study using reference human pangenomes

(A) Comparison of the performance of different tools using GRCh38 as the reference for structural variation detection using simulated data with different sequencing depths. (B) Effect of the completeness of the graph-modeled pangenome on its performance in detecting structural variants. The x-axis represents the number of samples to construct the graph-modeled pangenome. The five samples used for evaluation were excluded from the samples used to construct the five graph pangenomes. (C) Flowchart of the evaluation of different reference genomes and variant identification tools using sequencing data from the GIAB HG002 sample. Different colors represent different identification pipelines. (D) Performance evaluation results for variant identification using different reference genomes.

(A) Overlap of GRCh38-based SVs and GCPan-based SVs in the five simulated samples (SimuA). (B) Example of insertion that was detected in GRCh38 but not in GCPan. (C) Example of deletion that was detected using GRCh38 but not using GCPan. (B, C) Gray bars in (B, C) represent the alignment of reads at this position when using GRCh38 and GCPan as the reference genomes, respectively.

(A) 23 genes with mutation rates differing by more than 5% in 185 samples using the three reference genomes. The y-axis represents the number of mutations per gene in 185 samples. (B) TMBs in different cohorts. The three bolded black cohorts are our gastric cancer data using three reference genomes. (C) Results of correlation tests between TMB and MSI with each phenotype. Continuous variable phenotypes (e.g., age and tumor diameter) were subjected to Spearman’s correlation test using calculated values of TMB and MSI, and other types of phenotypes were subjected to Fisher’s exact test using state values of TMB and MSI (TMB-H/TMB-L, MSI-H/ MSI-L) for Fisher’s exact test. Each grid color corresponds to the negative logarithmic value of the P-value of the correlation test. In the figure, “*” indicates that the P-value is between 0.05 and 0.01, “**” indicates that the P-value is between 0.01 and 0.001, and “***” indicates that the P-value is less than 0.001, and unlabeled positions indicate that the correlation is not significant. (D) Sample distribution of TMB-H, TMB-L and MSI-H, MSI-L/MSS in the subtypes of location, Borrmann, and Lauren.

(A) Genes significantly related to phenotypes using GRCh38. (B) Genes significantly related to phenotypes using GCPan. (C) Genes significantly related to phenotypes using GGCPan. In the figure, “*” indicates that the P-value is between 0.05 and 0.01, “**” indicates that the P-value is between 0.01 and 0.001, and “***” indicates that the P-value is less than 0.001, and unlabeled positions indicate that the correlation is not significant.