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Many large-scale approaches do not explicitly account for phylogenetic relatedness between genomes which can inflate support for associations that are simply shared by close relatives. To address this, we introduce a scalable framework that clusters gene-family occurrences by genomic neighborhood and counts co-occurrences across distinct genomic contexts, reducing redundancy from vertical inheritance and uneven database sampling without explicit phylogenetic reconstruction. Applied to 32\u2009791 RefSeq genomes comprising 123 million genes, this approach identifies 15 million syntons across 779\u2009000 synton families, characterizing their diversity and revealing structured associations among antiphage defense systems. Leveraging this context-aware framework, we also introduce context residual entropy to quantify gene families neighborhood variability. By prioritizing independent evolutionary events over redundant genome-level counts, our approach provides a scalable, phylogenetic tree-free view of modular organization across bacterial genomes.<\/jats:p>","DOI":"10.1093\/femsml\/uqag033","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:52:54Z","timestamp":1788616374000},"source":"Crossref","is-referenced-by-count":0,"title":["Characterization of syntons across bacterial genomes using non-redundant genomic contexts"],"prefix":"10.1093","volume":"7","author":[{"given":"Alexandre","family":"Herv\u00e9","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris-Cit\u00e9, CNRS UMR3525, Molecular Diversity of Microbes , 75015 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Cury","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris-Cit\u00e9, CNRS UMR3525, Molecular Diversity of 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