{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:32:21Z","timestamp":1785411141646,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,17]]},"group-title":"Cell Biology","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["HL173490"],"award-info":[{"award-number":["HL173490"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Rational<\/jats:title>\n                  <jats:p>Cystic Fibrosis (CF) and Primary Ciliary Dyskinesia (PCD) are both inherited respiratory disorders that result in impaired mucociliary clearance, and chronic sinopulmonary disease. Although the current approach to PCD management is extrapolated from CF care, both conditions arise from distinct genetic and molecular mechanisms.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Here we performed a comparative transcriptomic analysis between CF and PCD to compare the cellular heterogeneity, molecular pathways and gene networks differences using publicly available sequencing data as well as those performed by our group. To explore gene regulatory networks, a pre-trained transformer model (scGPT) was fine-tuned using an integrated dataset, and differential attention analysis was conducted to identify genes and pathways with altered attention scores between the two conditions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The comparative transcriptomic analysis revealed distinct molecular signatures between PCD and CF, which differed from normal cells. In ciliated cells, differential gene expression and pathway investigation highlighted the NRF2 pathway\u2019s considerable overrepresentation in PCD compared to CF and healthy conditions. This observation was further supported by scGPT analysis, which revealed increased incoming attention to the NRF2 pathway markers. In secretory cells, PCD and CF exhibited increased immune and inflammatory signaling compared to controls. While similar inflammatory processes were active, results suggested a stronger inflammatory pattern in CF secretory cells compared to PCD and confirmed the activation of the unfolded protein response (UPR) pathway.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings highlight the different molecular signatures between both conditions and the need for unique approaches to management in PCD compared to CF.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.17.688876","type":"posted-content","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T23:55:21Z","timestamp":1763596521000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparative Single-Cell Transcriptomics Uncovers Shared and Distinct Molecular Signatures in Cystic Fibrosis and Primary Ciliary Dyskinesia"],"prefix":"10.64898","author":[{"given":"Nicholas","family":"Hadas","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang Kyaw","family":"Twan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shambhawee","family":"Neupane","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, 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