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While approximating vertical evolution through this approach has proven exceptionally valuable for understanding pathogen dynamics, it excludes a fundamental dimension of bacterial evolution\u2014horizontal gene transfer. Incorporating the accessory genome is the logical remediation and has recently shown promise in expanding epidemiological resolution for enteric pathogens. Employing\n                      <jats:italic>k<\/jats:italic>\n                      -mer-based Jaccard index analysis, and a novel genome length distance metric, we computed pangenome (i.e., core and accessory) relatedness for the globally important pathogen\n                      <jats:italic>Salmonella enterica<\/jats:italic>\n                      serotype Typhi (Typhi), and graphically express both vertical (homology-by-descent) and horizontal (homology-by-admixture) evolutionary relationships in a reticulate network of over 2,200 U.S. Typhi genomes. This analysis revealed non-random structure in the Typhi pangenome that is driven predominantly by the gain and loss of mobile genetic elements, confirming and expanding upon known epidemiological patterns, revealing novel plasmid dynamics, and identifying avenues for further genomic epidemiological exploration. With an eye to public health application, this work adds important biological context to the rapidly improving ways of analyzing bacterial genetic data and demonstrates the value of the accessory genome to infer pathogen epidemiology and evolution.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Given bacterial evolution occurs in both vertical and horizontal dimensions, inclusion of both core and accessory genetic material (i.e., the pangenome) is a logical step toward a more thorough understanding of pathogen dynamics. With an eye to public, and indeed, global health relevance, we couple contemporary tools for genomic analysis with decades of research on mobile genetic elements to demonstrate the value of the pangenome, known and unknown, annotated, and hypothetical, for stratification of\n                        <jats:italic>Salmonella enterica<\/jats:italic>\n                        serovar Typhi (Typhi) populations. We confirm and expand upon what is known about Typhi epidemiology, plasmids, and antimicrobial resistance dynamics, and offer new avenues of exploration to further deduce Typhi ecology and evolution, and ultimately to reduce the incidence of human disease.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.00365-24","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T09:00:23Z","timestamp":1721984423000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Mobile genetic elements define the non-random structure of the\n                    <i>Salmonella enterica<\/i>\n                    serovar Typhi pangenome"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2295-1563","authenticated-orcid":false,"given":"Arancha","family":"Pe\u00f1il-Celis","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria, (CSIC, Universidad de Cantabria), Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin A.","family":"Tagg","sequence":"additional","affiliation":[{"name":"Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-7930","authenticated-orcid":true,"given":"Hattie E.","family":"Webb","sequence":"additional","affiliation":[{"name":"Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Redondo-Salvo","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria, (CSIC, Universidad de Cantabria), Santander, Spain"},{"name":"Biomar Microbial Technologies, Leo\u0301n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Francois Watkins","sequence":"additional","affiliation":[{"name":"Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Vielva","sequence":"additional","affiliation":[{"name":"Departamento de Ingenier\u00eda de las Comunicaciones, Universidad de Cantabria, Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsey","family":"Griffin","sequence":"additional","affiliation":[{"name":"Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"},{"name":"Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"},{"name":"ASRT, Inc., Suwanee, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8514-5118","authenticated-orcid":true,"given":"Jason P.","family":"Folster","sequence":"additional","affiliation":[{"name":"Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-5428","authenticated-orcid":true,"given":"M. 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