Large-scale capsule genotype nomenclature and visualization for deciphering cps locus evolution and variation of Streptococcus pneumoniae

The pneumococcal capsular polysaccharide synthesis (cps) gene locus undergoes continuous dynamic evolution, with critical variations potentially driving vaccine escape. However, current epidemiological surveillance lacks high-throughput analytical capability for cps locus architecture and evolutionary dynamics. Here we introduce Pneumo-Typer, a high-throughput tool enabling automated pneumococcal capsule genotype (CapT) nomenclature and visualization while integrating serotype and sequence type (ST/cgST) prediction directly from assembled whole-genome sequencing data. Performance evaluations demonstrate this integrated framework facilitates comprehensive analysis of CapT evolution and variation: i) Elucidation of multi-serotype serogroup formation through CapT evolutionary trajectory analysis within and across serotypes, revealing cps locus gene-flow patterns; ii) Identification of conserved CapT-ST correspondence reflecting vertical inheritance constraints of CapTs within lineages; and iii) Detection of CapT variations driving potentialcapsule antigenic shifts, underscoring how incorporating CapT variants into vaccine design represents a promising complementary strategy to enhance coverage. Besides, Pneumo-Typer achieves high-fidelity serotype prediction (98.44% accuracy), with serotype-ST association analyses and CapT visualization features enabling robust serotype validation. In conclusion, by integrating CapT characterization into surveillance frameworks, Pneumo-Typer enables precise monitoring of cps locus evolution and variation while supporting CapT-driven vaccine optimization strategies.