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Efforts to improve diagnostics center around the development of molecular diagnostics (MDx), but due to deep tissue sequestration and the lack of persistent bacteremias, even MDx assays suffer from a lack of sensitivity. Additionally, the extensive genomic heterogeneity among isolates, even within the same species, contributes to the lack of assay sensitivity, as single target assays, whether nucleic acid-based or serologically based, cannot provide universal coverage. This within-species heterogeneity is partly due to differences in replicon repertoires and genomic structures that have likely arisen to support the complex\n                      <jats:italic toggle=\"yes\">Borreliaceae<\/jats:italic>\n                      life cycle necessary for these parasites to survive in multiple hosts, each with unique immune responses. We constructed a\n                      <jats:italic toggle=\"yes\">Borreliaceae<\/jats:italic>\n                      family-level pan-genome and characterized the phylogenetic relationships among the constituent taxa, which supports the recent, although contested, taxonomy of splitting the family into at least two genera. Gene content profiles were created for the majority of the\n                      <jats:italic toggle=\"yes\">Borreliaceae<\/jats:italic>\n                      replicons, providing for the first time their unambiguous molecular typing. Our characterization of the\n                      <jats:italic toggle=\"yes\">Borreliaceae<\/jats:italic>\n                      pan-genome supports the splitting of the former\n                      <jats:italic toggle=\"yes\">Borrelia<\/jats:italic>\n                      genus into two genera and provides for the phylogenetic placement of several non-species designated isolates. Mining this family-level pan-genome will enable the development of precision diagnostics corresponding to gene content-driven clinical outcomes while also providing targets for interventions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Using whole genome sequencing, we demonstrated that the bacteria that are transmitted by ticks and other arthropod vectors that cause Lyme disease and relapsing fevers, while related, do not belong within the same genus classification. In addition, through characterization of their highly atypical genomic structure, we were able to develop a genetic typing system that will help with future studies of how they cause disease while also providing targets for medical interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00943-25","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T09:00:17Z","timestamp":1746608417000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of the family-level\n                    <i>Borreliaceae<\/i>\n                    pan-genome and development of an episomal typing protocol"],"prefix":"10.1128","volume":"16","author":[{"given":"Kalya M.","family":"Socarras","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bdffz58","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Genomic Sciences, Institute for Molecular 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