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The opportunistic pathogen\n                    <jats:italic>\n                      <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2553\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:ext-link>\n                      <\/jats:named-content>\n                    <\/jats:italic>\n                    (\n                    <jats:italic>Pa<\/jats:italic>\n                    ) dominates airway infections in most CF adults. Here we hypothesized that within\u2013host genetic variation of\n                    <jats:italic>Pa<\/jats:italic>\n                    populations would be associated with lung disease severity. To quantify\n                    <jats:italic>Pa<\/jats:italic>\n                    genetic variation within CF sputum samples, we used deep amplicon sequencing (AmpliSeq) of 209\n                    <jats:italic>Pa<\/jats:italic>\n                    genes previously associated with pathogenesis or adaptation to the CF lung. We trained machine learning models using\n                    <jats:italic>Pa<\/jats:italic>\n                    single nucleotide variants (SNVs), microbiome diversity data and clinical factors to classify lung disease severity at the time of sputum sampling, and to predict lung function decline after 5\u2009years in a cohort of 54 adult CF patients with chronic\n                    <jats:italic>Pa<\/jats:italic>\n                    infection. Models using\n                    <jats:italic>Pa<\/jats:italic>\n                    SNVs alone classified lung disease severity with good sensitivity and specificity (area under the receiver operating characteristic curve: AUROC=0.87). Models were less predictive of lung function decline after 5\u2009years (AUROC=0.74) but still significantly better than random. The addition of clinical data, but not sputum microbiome diversity data, yielded only modest improvements in classifying baseline lung function (AUROC=0.92) and predicting lung function decline (AUROC=0.79), suggesting that\n                    <jats:italic>Pa<\/jats:italic>\n                    AmpliSeq data account for most of the predictive value. Our work provides a proof of principle that\n                    <jats:italic>Pa<\/jats:italic>\n                    genetic variation in sputum tracks lung disease severity, moderately predicts lung function decline and could serve as a disease biomarker among CF patients with chronic\n                    <jats:italic>Pa<\/jats:italic>\n                    infections.\n                  <\/jats:p>","DOI":"10.1099\/mgen.0.000981","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T11:18:22Z","timestamp":1681384702000},"source":"Crossref","is-referenced-by-count":3,"title":["Single nucleotide variants in Pseudomonas aeruginosa populations from sputum correlate with baseline lung function and predict disease progression in individuals with cystic fibrosis"],"prefix":"10.1099","volume":"9","author":[{"given":"Morteza M.","family":"Saber","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannik","family":"Donner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Levade","sequence":"additional","affiliation":[{"name":"Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Acosta","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Disease, University of Calgary, Calgary, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Parkins","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary, Calgary, AB, Canada"},{"name":"Department of Microbiology, Immunology and Infectious Disease, University of Calgary, Calgary, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Boyle","sequence":"additional","affiliation":[{"name":"Integrative Systems Biology Institute, University of Laval, Qu\u00e9bec, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger C.","family":"Levesque","sequence":"additional","affiliation":[{"name":"Integrative Systems Biology Institute, University of Laval, Qu\u00e9bec, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Meakins Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada"},{"name":"Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, QC, Canada"},{"name":"Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6819-8699","authenticated-orcid":false,"given":"B. 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