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Prospective monitoring, in which samples are continuously added and compared to previous samples, can generate more actionable information. To enable prospective pathogen comparison, genomic relatedness metrics based on single-nucleotide differences must be consistent across time, efficient to compute and reliable for a large variety of samples. The choice of genomic regions to compare, <jats:italic>i.e<\/jats:italic>., the <jats:italic>core genome<\/jats:italic>, is critical to obtain a good metric. We propose a novel core genome method that selects conserved sequences in the reference genome by comparing its k-mer content to that of publicly available genome assemblies. The conserved-sequence genome is sample set-independent, which enables prospective pathogen monitoring. Based on clinical data sets of 3436 <jats:italic>S. aureus<\/jats:italic>, 1362 <jats:italic>K. pneumoniae<\/jats:italic> and 348 <jats:italic>E. faecium<\/jats:italic> samples, ROC curves demonstrate that the conserved-sequence genome disambiguates same-patient samples better than a core genome consisting of conserved genes. The conserved-sequence genome confirms outbreak samples with high sensitivity: in a set of 2335 <jats:italic>S. aureus<\/jats:italic> samples, it correctly identifies 44 out of 44 known outbreak samples, whereas the conserved-gene method confirms 38 known outbreak samples.<\/jats:p>","DOI":"10.1038\/s41598-019-44189-0","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T10:03:50Z","timestamp":1558692230000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A core genome approach that enables prospective and dynamic monitoring of infectious outbreaks"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4934-0300","authenticated-orcid":false,"given":"Helen van","family":"Aggelen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raivo","family":"Kolde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hareesh","family":"Chamarthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Loving","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III.","given":"John T.","family":"Fallon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Fortunato-Habib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Carmona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9830-5459","authenticated-orcid":false,"given":"Brian D.","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"44189_CR1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.cmi.2017.11.001","volume":"24","author":"JWA Rossen","year":"2018","unstructured":"Rossen, J. 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H.vA. and B.D.G. have submitted a patent application on the core genome methodology (62\/684323, 06\/13\/2018). J.T.F., W.H. and G.W. have received funding from Philips Research towards the work described herein and other work related to infectious disease research.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7808"}}