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

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.