Extended Data Fig. 4: Heterogeneity of baseline gut microbial compositions across meta-analysis cohorts.

a, Proportion of quality-controlled paired-end reads aligned by Bowtie 2 (red), and ultimately used for abundance estimation after stringent filtering (cyan). Organised by study (2017_FRANKEL n = 39, 2018_MATSON n = 39, 2021_ANDREWS n = 46, LEE n = 165, 2022_MCCULLOCH n = 37, 2022_ 2022_SIMPSON n = 38, CA209-538 n = 106). Boxplot central line= median, box limits= upper and lower quartiles, and whiskers= 1.5x interquartile range. Median printed within each boxplot. b, Proportion of explained variance (R²) of microbial composition by metadata variables (grouped into ‘exposome’, ‘technical’ and ‘tumour’ categories. R² values (printed on bar) calculated using PERMANOVA (9999 permutations). c, PCA plot of samples by CLR-transformed abundances (Aitchison’s distance), with points coloured by sample city (the variable explaining the most variance). Ellipses depict 0.8 of each group’s multivariate t-distribution. PERMANOVA p-value and R² using 9999 permutations printed. d, PCA plot of samples by CLR-transformed abundances (Aitchison’s distance), with points coloured by extraction kit (the variable explaining the second-most variance). Ellipses depict 0.8 of each group’s multivariate t-distribution. PERMANOVA p-value and R² using 9999 permutations printed. Acronyms: ICB= immune checkpoint blockade, PCo= principle coordinate.