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This study provides evolutionary classification of proteins from\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    pangenome. We classified 17,238 domains from 13,147 proteins from 79,758\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    strains and studied in detail domains of 272 proteins from 14 characterized\n                    <jats:italic>Salmonella<\/jats:italic>\n                    pathogenicity islands (SPIs). Among SPIs-related proteins, 90 proteins function in the secretion machinery. 41% domains of SPI proteins have no previous sequence annotation. By comparing clinical and environmental isolates, we identified 3682 proteins that are overrepresented in clinical group that we consider as potentially pathogenic. Among domains of potentially pathogenic proteins only 50% domains were annotated by sequence methods previously. Moreover, 36% (1330 out of 3682) of potentially pathogenic proteins cannot be classified into Evolutionary Classification of Protein Domains database (ECOD). Among classified domains of potentially pathogenic proteins the most populated homology groups include helix-turn-helix (HTH), Immunoglobulin-related, and P-loop domains-related. Functional analysis revealed overrepresentation of these protein in biological processes related to viral entry into host cell, antibiotic biosynthesis, DNA metabolism and conformation change, and underrepresentation in translational processes. Analysis of the potentially pathogenic proteins indicates that they form 119 clusters or novel potential pathogenicity islands (NPPIs) within the\n                    <jats:italic>Salmonella<\/jats:italic>\n                    genome, suggesting their potential contribution to the bacterium\u2019s virulence. One of the NPPIs revealed significant overrepresentation of potentially pathogenic proteins. Overall, our analysis revealed that identified potentially pathogenic proteins are poorly studied.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-60991-x","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T17:04:16Z","timestamp":1716915856000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Structure classification of the proteins from Salmonella enterica pangenome revealed novel potential pathogenicity islands"],"prefix":"10.1038","volume":"14","author":[{"given":"Kirill E.","family":"Medvedev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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