{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:23:57Z","timestamp":1776129837721,"version":"3.50.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0224615","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T17:28:18Z","timestamp":1572629298000},"page":"e0224615","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hidden noise in immunologic parameters might explain rapid progression in early-onset periodontitis"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-7803","authenticated-orcid":true,"given":"George","family":"Papantonopoulos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8267-8987","authenticated-orcid":true,"given":"Chryssa","family":"Delatola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiso","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6052-041X","authenticated-orcid":true,"given":"Marja L.","family":"Laine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno G.","family":"Loos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2019,11,1]]},"reference":[{"key":"pone.0224615.ref001","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.cden.2015.06.005","article-title":"What is the contribution of genetics to periodontal risk?","volume":"59","author":"BG Loos","year":"2015","journal-title":"Dent Clin North Am"},{"key":"pone.0224615.ref002","article-title":"The role of inflammation and genetics in periodontal disease","author":"BG Loos","year":"2000","journal-title":"Periodontol"},{"key":"pone.0224615.ref003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12047","article-title":"Modifiable risk factors in periodontitis: at the intersection of aging and disease","volume":"64","author":"AM Reynolds","year":"2014","journal-title":"Periodontol 2000"},{"key":"pone.0224615.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1142\/8260","volume-title":"Foundations of complex systems: emergence, information and prediction","author":"G Nicolis","year":"2012"},{"key":"pone.0224615.ref005","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1902\/jop.2012.120444","article-title":"Aggressive periodontitis defined by recursive partitioning analysis of immunologic factors","volume":"84","author":"G Papantonopoulos","year":"2013","journal-title":"J Periodontol"},{"issue":"3","key":"pone.0224615.ref006","doi-asserted-by":"crossref","first-page":"e89757","DOI":"10.1371\/journal.pone.0089757","article-title":"Artificial neural networks for the diagnosis of aggressive periodontitis trained by immunologic parameters","volume":"9","author":"G Papantonopoulos","year":"2014","journal-title":"PLOS ONE"},{"key":"pone.0224615.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","article-title":"Development of a classification system for periodontal diseases and conditions","volume":"4","author":"GC Armitage","year":"1999","journal-title":"Ann Periodontol"},{"key":"pone.0224615.ref008","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1600-0757.2005.00127.x","article-title":"Purpose and problems of periodontal disease classification","volume":"39","author":"U Van der Velden","year":"2005","journal-title":"Periodontol 2000"},{"issue":"Suppl20","key":"pone.0224615.ref009","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.1111\/jcpe.12942","article-title":"Classification and diagnosis of aggressive periodontitis","volume":"45","author":"DH Fine","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"3","key":"pone.0224615.ref010","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/hmg\/ddp508","article-title":"A genome-wide association study identifies GLT6D1 as a susceptibility locus for periodontitis","volume":"19","author":"AS Schaefer","year":"2010","journal-title":"Hum Mol Genet"},{"key":"pone.0224615.ref011","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1177\/0022034513506011","article-title":"Molecular Differences between Chronic and Aggressive Periodontitis","volume":"92","author":"M Kebschull","year":"2013","journal-title":"J Dent Res"},{"issue":"Suppl 20","key":"pone.0224615.ref012","doi-asserted-by":"crossref","first-page":"S149","DOI":"10.1111\/jcpe.12945","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"45","author":"MS Tonetti","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"Suppl 20","key":"pone.0224615.ref013","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1111\/jcpe.12946","article-title":"Periodontitis: Consensus report of Workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri\u2010Implant Diseases and Conditions","volume":"45","author":"PN Papapanou","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"Suppl 20","key":"pone.0224615.ref014","doi-asserted-by":"crossref","first-page":"S130","DOI":"10.1111\/jcpe.12944","article-title":"Age\u2010dependent distribution of periodontitis in two countries: findings from NHANES 2009\u20102014 and SHIP\u2010TREND 2008\u20102012","volume":"45","author":"M Billings","year":"2018","journal-title":"J Clin Periodontol"},{"key":"pone.0224615.ref015","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/j.1600-051X.1982.tb02108.x","article-title":"Patterns of progression and regression of advanced destructive periodontal disease","volume":"9","author":"JM Goodson","year":"1982","journal-title":"J Clin Periodontol"},{"key":"pone.0224615.ref016","first-page":"216","volume":"135","author":"A Raj","year":"2008","journal-title":"Stochastic gene expression and its consequences Cell"},{"key":"pone.0224615.ref017","doi-asserted-by":"crossref","first-page":"20131104","DOI":"10.1098\/rspb.2013.1104","article-title":"Adaptive noise","volume":"280","author":"M Viney","year":"2013","journal-title":"Proc R Soc B"},{"key":"pone.0224615.ref018","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrg3888","article-title":"Random monoallelic expression of autosomal genes: stochastic transcription and allele-level regulation","volume":"16","author":"B Reinius","year":"2015","journal-title":"Nat Rev Genet"},{"key":"pone.0224615.ref019","doi-asserted-by":"crossref","first-page":"8372","DOI":"10.1073\/pnas.0507818103","article-title":"Stochastic models for regulatory networks of the genetic toggle switch","volume":"103","author":"T Tian","year":"2006","journal-title":"Proc Nat Acad Sci"},{"key":"pone.0224615.ref020","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1600-051X.1986.tb01487.x","article-title":"Natural history of periodontal disease in man. Rapid, moderate and no loss of attachment in Sri Lankan laborers 14 to 46 years of age","volume":"13","author":"H L\u00f6e","year":"1986","journal-title":"J Clin Periodontol"},{"key":"pone.0224615.ref021","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1902\/jop.2001.72.4.425","article-title":"Heterogeneity of host immunologic risk factors in patients with aggressive periodontitis","volume":"72","author":"K Takahashi","year":"2001","journal-title":"J Periodontol"},{"key":"pone.0224615.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/1541880.1541882","article-title":"Anomaly detection: A survey","volume":"9","author":"V Chandola","year":"2009","journal-title":"ACM Comp Surv"},{"key":"pone.0224615.ref023","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1111\/jcpe.12797","article-title":"At least three phenotypes exist among periodontitis patients","volume":"44","author":"C Delatola","year":"2017","journal-title":"J Clin Periodontol"},{"issue":"6163","key":"pone.0224615.ref024","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1126\/science.1242975","article-title":"Genetic determinants and cellular constraints in noisy gene expression","volume":"342","author":"A Sanchez","year":"2013","journal-title":"Science"},{"key":"pone.0224615.ref025","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.tem.2016.06.008","article-title":"The emerging role of epigenetics in inflammation and immunometabolism","volume":"27","author":"S Raghuraman","year":"2016","journal-title":"Trends Endocrinol Metab"},{"key":"pone.0224615.ref026","first-page":"1157","article-title":"An introduction to variable and feature selection","volume":"3","author":"I Guyon","year":"2003","journal-title":"J Mach Learn Res"},{"key":"pone.0224615.ref027","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41579-018-0089-x","article-title":"The oral microbiota: dynamic communities and host interaction","volume":"16","author":"RJ Lamont","year":"2018","journal-title":"Nat Microbiol"},{"key":"pone.0224615.ref028","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1177\/0022034510376402","article-title":"Destructive and protective roles of cytokines in periodontitis: A re-appraisal from host defense and tissue destruction viewpoints","volume":"89","author":"GP Garlet","year":"2010","journal-title":"J Dent Res"},{"key":"pone.0224615.ref029","doi-asserted-by":"crossref","first-page":"188","DOI":"10.4161\/21505594.2014.982428","article-title":"Aggregatibacter Actinomycetemcomitans: Virulence of its leukotoxin and association with aggressive periodontitis","volume":"6","author":"HC \u00c5berg","year":"2015","journal-title":"Virulence"},{"issue":"9608","key":"pone.0224615.ref030","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0140-6736(08)60135-X","article-title":"Risk of aggressive periodontitis in adolescent carriers of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans in Morocco: a prospective longitudinal cohort study","volume":"371","author":"D Haubek","year":"2008","journal-title":"Lancet"},{"issue":"Suppl 3","key":"pone.0224615.ref031","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1034\/j.1600-051X.29.s3.1.x","article-title":"Can presence or absence of periodontal pathogens distinguish between subjects with chronic and aggressive periodontitis? A systematic review","volume":"29","author":"A Mombelli","year":"2002","journal-title":"J Clin Periodontol"},{"key":"pone.0224615.ref032","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/jcpe.13046","article-title":"An appraisal of the role of specific bacteria in the initial pathogenesis of periodontitis","volume":"46","author":"PM Bartold","year":"2019","journal-title":"J Clin Periodontol"},{"key":"pone.0224615.ref033","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1038\/s41598-019-41882-y","article-title":"Enrichment of periodontal pathogens from the biofilms of healthy adults","volume":"9","author":"M Naginyte","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0224615.ref034","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.intimp.2013.06.034","article-title":"Neutrophil cell surface receptors and their intercellular signal transduction pathways","volume":"17","author":"K Futosi","year":"2013","journal-title":"Inter Immunopharm"},{"key":"pone.0224615.ref035","first-page":"256","volume-title":"Clinical Periodontology and Implant Dentistry","author":"JG Seymour","year":"2015"},{"issue":"22","key":"pone.0224615.ref036","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1001\/jama.2016.17216","article-title":"Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs","volume":"316","author":"V Gulshan","year":"2016","journal-title":"JAMA"},{"issue":"3","key":"pone.0224615.ref037","doi-asserted-by":"crossref","first-page":"e0214365","DOI":"10.1371\/journal.pone.0214365","article-title":"Prediction of premature all-cause mortality: A prospective general population cohort study comparing machine-learning and standard epidemiological approaches","volume":"14","author":"SF Weng","year":"2019","journal-title":"PLOS ONE"},{"issue":"4","key":"pone.0224615.ref038","first-page":"32","article-title":"Anomaly detection in data mining","volume":"7","author":"JD Parmar","year":"2017","journal-title":"IJARCCE"},{"key":"pone.0224615.ref039","doi-asserted-by":"crossref","first-page":"e0152173","DOI":"10.1371\/journal.pone.0152173","article-title":"A comparative evaluation of unsupervised anomaly detection algorithms for multivariate data","volume":"11","author":"M Goldstein","year":"2016","journal-title":"PLOS ONE"},{"key":"pone.0224615.ref040","doi-asserted-by":"crossref","unstructured":"Lakhina A, Crovella M, Diot C. Diagnosing network-wide traffic anomalies. In: Proceedings of the 2004 conference on Applications, technologies, architectures, and protocols for computer communications. Portland; Oregon USA, 2004: 1\u201323.","DOI":"10.1145\/1015467.1015492"},{"key":"pone.0224615.ref041","first-page":"11","article-title":"A two-step method for clustering mixed categorical and numerical data","volume":"13","author":"M-Y Shih","year":"2010","journal-title":"Tamkang J Sci Eng"},{"key":"pone.0224615.ref042","unstructured":"Breunig MM, Kriegel HP, Ng RT, Sander J. LOF: Identifying Density-Based Local Outliers. In: Proceedings of the 2000 ACM SIGMOD International Conference on Management of Data. Dallas, Texas; ACM Press, 2000: 93\u2013104."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0224615","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T20:50:54Z","timestamp":1588971054000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0224615"}},"subtitle":[],"editor":[{"given":"\u00d6zlem","family":"Yilmaz","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,11,1]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0224615","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,1]]}}}