{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:46:06Z","timestamp":1791812766417,"version":"4.3.4"},"reference-count":56,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1230764"],"award-info":[{"award-number":["1230764"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["13250023"],"award-info":[{"award-number":["13250023"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["21201171"],"award-info":[{"award-number":["21201171"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Bifidobacterium<\/jats:italic>\n                      species are important microorganisms in the infant gut microbiota displaying substantial genomic diversity, yet how this variability is reflected in transcriptional regulatory architecture remains an open question. Here, we integrated pangenome analysis with transcription factor binding site inference and network-based approaches to compare regulatory architectures across\n                      <jats:italic toggle=\"yes\">Bifidobacterium longum<\/jats:italic>\n                      subsp.\n                      <jats:italic toggle=\"yes\">infantis<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Bifidobacterium breve<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">B. longum<\/jats:italic>\n                      subsp.\n                      <jats:italic toggle=\"yes\">longum<\/jats:italic>\n                      using over 300 high-quality genomes. All three species exhibited open pangenomes, with regulatory interactions frequently involving accessory genes. Inferred network metrics were compared with score-randomized controls across motif-score thresholds. Increasing score stringency reduced network size while increasing the number of detected communities, indicating greater fragmentation of the retained networks rather than a measured increase in modularity.\n                      <jats:italic toggle=\"yes\">NrdR<\/jats:italic>\n                      showed an intermediate overlap in the Clusters of Orthologous Groups (COG) category sets represented among its predicted targets and species-dependent target prevalence. HMO-related regulators (\n                      <jats:italic toggle=\"yes\">FucR<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">NanR<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">NagR<\/jats:italic>\n                      ) differed descriptively between\n                      <jats:italic toggle=\"yes\">Bifidobacterium infantis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">B. breve<\/jats:italic>\n                      , the two species included in the complete three-regulator comparison, in predicted target counts, represented COG category sets, and genomic-prevalence patterns; only\n                      <jats:italic toggle=\"yes\">FucR<\/jats:italic>\n                      showed a significant difference in accessory-target fraction. These findings identify species-dependent differences in predicted regulon composition and genomic prevalence and provide testable hypotheses about how regulatory architecture may relate to ecological specialization in the infant gut.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Bifidobacterium<\/jats:italic>\n                      species are among the most abundant microorganisms in the breast-fed infant gut microbiota, where they display distinct patterns of genomic diversification and host association. However, the transcriptional regulatory mechanisms underlying these species-specific differences remain incompletely characterized. Here, we reconstructed and compared genome-scale transcriptional regulatory networks across three infant-associated\n                      <jats:italic toggle=\"yes\">Bifidobacterium<\/jats:italic>\n                      species, integrating pangenome structure with transcription factor binding site inference across more than 300 genomes. Our analyses identified predicted regulatory interactions involving accessory genes and species-specific differences in network structure, regulon composition, and target prevalence. These associations provide hypotheses for experimental studies of how gene content and regulatory architecture may contribute to niche adaptation. This pangenome-scale framework can support the prioritization of regulatory hypotheses for future functional studies of infant-associated\n                      <jats:italic toggle=\"yes\">Bifidobacterium<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.01082-26","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:00:59Z","timestamp":1791810059000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Comparative transcriptional network analysis reveals ecological specialization in infant-associated species of\n                    <i>Bifidobacterium<\/i>"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0540-5773","authenticated-orcid":true,"given":"Felipe","family":"Melis-Arcos","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04teye511","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemical and Bioprocess Engineering, School of Engineering, Pontificia Universidad Cat\u00f3lica de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Arita","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02xg1m795","id-type":"ROR","asserted-by":"publisher"}],"name":"Bioinformation and DDBJ Center, National Institute of Genetics","place":["Mishima, 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