{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:20:33Z","timestamp":1792131633548,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001734","name":"University of Copenhagen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001734","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>\n                    Clinicians and researchers utilize subjective, clinical classification systems to stratify lower extremity ulcer infections for treatment and research. The purpose of this study was to examine whether these clinical classifications are reflected in the ulcer's transcriptome. RNA sequencing (RNA\u2010seq) was performed on biopsies from clinically infected lower extremity ulcers (n\u2009=\u200944). Resulting sequences were aligned to the host reference genome to create a transcriptome profile. Differential gene expression analysis and gene ontology (GO) enrichment analysis were performed between ulcer severities as well as between sample groups identified by k\u2010means clustering. Lastly, a support vector classifier was trained to estimate clinical infection score or k\u2010means cluster based on a subset of genes. Clinical infection severity did not explain the major sources of variability among the samples and samples with the same clinical classification demonstrated high inter\u2010sample variability. High proportions of bacterial RNA were identified in some samples, which resulted in a strong effect on transcription and increased expression of genes associated with immune response and inflammation. K\u2010means clustering identified two clusters of samples, one of which contained all of the samples with high levels of bacterial RNA. A support vector classifier identified a fingerprint of 20 genes, including immune\u2010associated genes such as\n                    <jats:italic>CXCL8<\/jats:italic>\n                    ,\n                    <jats:italic>GADD45B<\/jats:italic>\n                    , and\n                    <jats:italic>HILPDA<\/jats:italic>\n                    , which accurately identified samples with signs of infection\n                    <jats:italic>via<\/jats:italic>\n                    cross\u2010validation. This study identified a unique, host\u2010transcriptome signature in the presence of infecting bacteria, often incongruent with clinical infection\u2010severity classifications. This suggests that stratification of infection status based on a transcriptomic fingerprint may be useful as an objective classification method to classify infection severity, as well as a tool for studying host\u2013pathogen interactions.\n                  <\/jats:p>","DOI":"10.1111\/apm.13234","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T09:25:37Z","timestamp":1652520337000},"page":"524-534","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Transcriptomic fingerprint of bacterial infection in lower extremity ulcers"],"prefix":"10.1111","volume":"130","author":[{"given":"Blaine G.","family":"Fritz","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, Faculty of Health and Medical Science University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius B.","family":"Kirkegaard","sequence":"additional","affiliation":[{"name":"Niels Bohr Institute University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus Henrik","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Spine Diseases Institute for Inflammation Research Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Kirketerp\u2010M\u00f8ller","sequence":"additional","affiliation":[{"name":"Center for Wound Healing Bispebjerg Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Malone","sequence":"additional","affiliation":[{"name":"South West Sydney Limb Preservation and Wound Research Liverpool Hospital Sydney Australia"},{"name":"Infectious Diseases and Microbiology, School of Medicine Western Sydney University Sydney 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