{
  "abstract": "Background Streptococcus anginosus is an emerging pathogen involved in gastric carcinogenesis, yet GC-associated genomic features remain poorly characterized. This study aimed to characterize the genomic landscape of S. anginosus to identify specific genetic features or variations associated with its potential tumor-promoting role.Methods We collected 85 S. anginosus genomes: seven derived from gastric cancer (GC) patients (Zhou et al., 2026), one from a GC patient (Yuan et al., 2024), and 77 genomes (28 NCBI reference genomes and 49 from healthy individuals). Genomes were annotated using Prokka, followed by pangenome analysis using Panaroo. Phylogeny was reconstructed using IQ-TREE based on core-genome alignment. Methionine biosynthesis (KEGG module M00017) was profiled using HMMER/KofamScan. Unitig-based genome-wide association analysis (pyseer) identified GC-enriched sequence variants upstream of metE. TmpC (a surface-exposed lipoprotein) orthologs and virulence factor (VF) profiles (ABRicate/VFDB) were compared across groups to assess differences in pathogenic potential.Results The S. anginosus pangenome was ‘open (reflecting genomic plasticity)’, comprising 6,792 genes (990 core, 327 soft-core, 811 shell, and 4,664 cloud genes) (IDDF2026-ABS-0536 Figure 1). GC-associated strains were distributed across multiple phylogenetic lineages rather than forming a single clade, indicating genomic diversity. The tmpC sequences and VF profiles, including genes for adhesion (fbp54, pavA), immune evasion (cps4A, cps4B, and cps4D), and stress resistance (psaA), were nearly identical between the groups, with no GC-exclusive virulence markers identified (IDDF2026-ABS-0536 Figure 2). All seven pathway genes were present in over >88% of strains, indicating broad conservation of the methionine biosynthesis pathway across all isolates (IDDF2026-ABS-0536 Figure 3). We identified a specific GC-enriched motif (Motif A) upstream of the metE gene. This motif was present in 62.5% (5/8) of GC strains compared to only 11.7% (9/77) of non-GC strains ‘(OR 12.6, P=0.0025; n=8 GC strains)’, suggesting potential regulatory divergence at this locus (IDDF2026-ABS-0536 Figure 3(c)).Conclusions GC-associated S. anginosus strains exhibit significant genomic diversity and share a conserved core of virulence and metabolic factors with non-GC strains. However, the identification of a GC-enriched regulatory motif near the metE gene suggests that subtle variations in metabolic regulation, rather than the presence of unique virulence genes, may contribute to its role in the gastric tumor microenvironment.Abstract IDDF2026-ABS-0536 Figure 1Abstract IDDF2026-ABS-0536 Figure 2Abstract IDDF2026-ABS-0536 Figure 3",
  "authors": [
    {
      "affiliations": [
        "BGI Genomics, Shenzhen, China"
      ],
      "name": "Hasnain Jadoon"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Li-Cong Zhao"
    },
    {
      "affiliations": [
        "BGI Research, Shenzhen, China"
      ],
      "name": "Yuanqiang Zou"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Cheng-Bei Zhou"
    },
    {
      "affiliations": [
        "BGI Genomics, Shenzhen, China"
      ],
      "name": "Youwen Qin"
    }
  ],
  "title": "IDDF2026-ABS-0536 Comparative genomic analysis of gastric cancer-associated streptococcus anginosus strains",
  "uid": "3a00cf3f-807c-575e-9d26-89c87da2b3ad"
}