{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T14:27:09Z","timestamp":1778509629911,"version":"3.51.4"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01 DC015004 , R01 DC000129 , T32 DC012280"],"award-info":[{"award-number":["R01 DC015004 , R01 DC000129 , T32 DC012280"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Otitis media (OM) is a leading cause of childhood hearing loss. Variants in <jats:italic>FUT2<\/jats:italic>, which encodes alpha-(1,2)-fucosyltransferase, were identified to increase susceptibility to OM, potentially through shifts in the middle ear (ME) or nasopharyngeal (NP) microbiotas as mediated by transcriptional changes. Greater knowledge of differences in relative abundance of otopathogens in carriers of pathogenic variants can help determine risk for OM in patients. In order to determine the downstream effects of <jats:italic>FUT2<\/jats:italic> variation, we examined gene expression in relation to carriage of a common pathogenic <jats:italic>FUT2<\/jats:italic> c.461G&amp;gt;A (p.Trp154*) variant using RNA-sequence data from saliva samples from 28 patients with OM. Differential gene expression was also examined in bulk mRNA and single-cell RNA-sequence data from wildtype mouse ME mucosa after inoculation with non-typeable <jats:italic>Haemophilus influenzae<\/jats:italic> (NTHi). In addition, microbiotas were profiled from ME and NP samples of 65 OM patients using 16S rRNA gene sequencing. In human carriers of the <jats:italic>FUT2<\/jats:italic> variant, <jats:italic>FN1, KMT2D, MUC16<\/jats:italic> and <jats:italic>NBPF20<\/jats:italic> were downregulated while <jats:italic>MTAP<\/jats:italic> was upregulated. Post-infectious expression in the mouse ME recapitulated these transcriptional differences, with the exception of <jats:italic>Fn1<\/jats:italic> upregulation after NTHi-inoculation. In the NP, Candidate Division TM7 was associated with wildtype genotype (FDR-adj-<jats:italic>p<\/jats:italic>=0.009). Overall, the <jats:italic>FUT2<\/jats:italic> c.461G&amp;gt;A variant was associated with transcriptional changes in processes related to response to infection and with increased load of potential otopathogens in the ME and decreased commensals in the NP. These findings provide increased understanding of how <jats:italic>FUT2<\/jats:italic> variants influence gene transcription and the mucosal microbiota, and thus contribute to the pathology of OM.<\/jats:p>","DOI":"10.3389\/fcimb.2021.798246","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:59:35Z","timestamp":1642139975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The FUT2 Variant c.461G&gt;A (p.Trp154*) Is Associated With Differentially Expressed Genes and Nasopharyngeal Microbiota Shifts in Patients With Otitis Media"],"prefix":"10.3389","volume":"11","author":[{"given":"Christina L.","family":"Elling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa A.","family":"Scholes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven-Olrik","family":"Streubel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric D.","family":"Larson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd M.","family":"Wine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tori C.","family":"Bootpetch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia J.","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Kofonow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel P.","family":"Gubbels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen P.","family":"Cass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles E.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herman A.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy D.","family":"Prager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel N.","family":"Frank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenny H.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman R.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen F.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regie Lyn P.","family":"Santos-Cortez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.12688\/wellcomeopenres.14636.2","article-title":"FUT2 Secretor Genotype and Susceptibility to Infections and Chronic Conditions in the ALSPAC Cohort","volume":"3","author":"Azad","year":"2018","journal-title":"Wellcome. Open Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3390\/genes12040468","article-title":"Kabuki Syndrome-Clinical Review With Molecular Aspects","volume":"12","author":"Boniel","year":"2021","journal-title":"Genes (Basel)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1177\/0022034519831671","article-title":"Saccharibacteria (TM7) in the Human Oral Microbiome","volume":"98","author":"Bor","year":"2019","journal-title":"J. Dent. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/jpc.12741","article-title":"Prevalence and Risk Factors for Parent-Reported Recurrent Otitis Media During Early Childhood in the Western Australian Pregnancy Cohort (Raine) Study","volume":"51","author":"Brennan-Jones","year":"2015","journal-title":"J. Paediatr. Child Health"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1111\/jpc.15370","article-title":"Otopathogen Interactions in the Nasopharynx of Children, and the Predictive Value of Nasopharyngeal Aspirate Culture for the Aetiology of Upper Respiratory Infections","volume":"57","author":"Browne","year":"2021","journal-title":"J. Paediatr. Child Health"},{"key":"B6","doi-asserted-by":"publisher","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS Catalog of Published Genome-Wide Association Studies, Targeted Arrays and Summary Statistics 2019","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1001\/jama.282.22.2125","article-title":"The Heritability of Otitis Media: A Twin and Triplet Study","volume":"282","author":"Casselbrant","year":"1999","journal-title":"JAMA"},{"key":"B8","doi-asserted-by":"publisher","first-page":"843","DOI":"10.21037\/atm-21-1392","article-title":"The Predictive Prognostic Values of CBFA2T3, STX3, DENR, EGLN1, FUT4, and PCDH7 in Lung Cancer","volume":"9","author":"Chen","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1111\/1523-1747.ep12500075","article-title":"Fibronectin and Fibrin Provide a Provisional Matrix for Epidermal Cell Migration During Wound Reepithelialization","volume":"79","author":"Clark","year":"1982","journal-title":"J. Invest. Dermatol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12500075","article-title":"Chemically Defined Media for Growth of Haemophilus Influenzae Strains","volume":"41","author":"Coleman","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1186\/s12864-016-3290-1","article-title":"ABO Antigen and Secretor Statuses Are Not Associated With Gut Microbiota Composition in 1,500 Twins","volume":"17","author":"Davenport","year":"2016","journal-title":"BMC Genomics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1078\/0171-9335-00104","article-title":"Cellular Invasion by Staphylococcus Aureus Involves a Fibronectin Bridge Between the Bacterial Fibronectin-Binding MSCRAMMs and Host Cell Beta1 Integrins","volume":"79","author":"Fowler","year":"2000","journal-title":"Eur. J. Cell Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1136\/jmedgenet-2020-106844","article-title":"Otitis Media Susceptibility and Shifts in the Head and Neck Microbiome Due to SPINK5 Variants","volume":"58","author":"Frank","year":"2021","journal-title":"J. Med. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/S0140-6736(21)00516-X","article-title":"Hearing Loss Prevalence and Years Lived With Disability 1990-2019: Findings From the Global Burden of Disease Study 2019","volume":"397","year":"2021","journal-title":"Lancet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00313","article-title":"Genomics of Otitis Media (OM): Molecular Genetics Approaches to Characterize Disease Pathophysiology","volume":"11","author":"Giese","year":"2020","journal-title":"Front. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/s12864-015-1475-7","article-title":"The Transcriptome of a Complete Episode of Acute Otitis Media","volume":"16","author":"Hernandez","year":"2015","journal-title":"BMC Genomics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1084\/jem.159.6.1618","article-title":"Fibronectin Enhances the Opsonic and Protective Activity of Monoclonal and Polyclonal Antibody Against Group B Streptococci","volume":"159","author":"Hill","year":"1984","journal-title":"J. Exp. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1002\/ajmg.a.30722","article-title":"Immune Abnormalities are a Frequent Manifestation of Kabuki Syndrome","volume":"135","author":"Hoffman","year":"2005","journal-title":"Am. J. Med. Genet. A."},{"key":"B20","doi-asserted-by":"publisher","first-page":"W627","DOI":"10.1093\/nar\/gki443","article-title":"VAMPIRE Microarray Suite: A Web-Based Platform for the Interpretation of Gene Expression Data","volume":"33","author":"Hsiao","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1017\/S0022215116009294","article-title":"Microbiology of Otitis Media in Indigenous Australian Children: Review","volume":"131","author":"Jervis-Bardy","year":"2017","journal-title":"J. Laryngol. Otol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00456-19","article-title":"Examining the Evidence for an Adult Healthy Middle Ear Microbiome","volume":"4","author":"Jervis-Bardy","year":"2019","journal-title":"mSphere"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","article-title":"Toward Understanding the Origin and Evolution of Cellular Organisms","volume":"28","author":"Kanehisa","year":"2019","journal-title":"Protein Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating Viruses and Cellular Organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"4640","DOI":"10.1074\/jbc.270.9.4640","article-title":"Sequence and Expression of a Candidate for the Human Secretor Blood Group Alpha(1,2)Fucosyltransferase Gene (FUT2). Homozygosity for an Enzyme-Inactivating Nonsense Mutation Commonly Correlates With the non-Secretor Phenotype","volume":"270","author":"Kelly","year":"1995","journal-title":"J. Biol. Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1097\/MLG.0b013e31806db531","article-title":"Mucin Gene Expression in Human Middle Ear Epithelium","volume":"117","author":"Kerschner","year":"2007","journal-title":"Laryngoscope"},{"key":"B28","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ijporl.2012.09.037","article-title":"A Novel Model of Spontaneous Otitis Media With Effusion (OME) in the Oxgr1 Knock-Out Mouse","volume":"77","author":"Kerschner","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.ijporl.2010.04.014","article-title":"Mucin Gene Expression and Mouse Middle Ear Epithelium","volume":"74","author":"Kerschner","year":"2010","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1096\/fj.08-119131","article-title":"Characterization of Exosome-Like Vesicles Released From Human Tracheobronchial Ciliated Epithelium: A Possible Role in Innate Defense","volume":"23","author":"Kesimer","year":"2009","journal-title":"FASEB J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e0134623","DOI":"10.1371\/journal.pone.0134623","article-title":"Secretor Status Is Strongly Associated With Microbial Alterations Observed During Pregnancy","volume":"10","author":"Kumar","year":"2015","journal-title":"PLoS One"},{"key":"B32","doi-asserted-by":"publisher","first-page":"10555","DOI":"10.1038\/s41598-017-11215-y","article-title":"A Cross-Sectional Comparative Study of Gut Bacterial Community of Indian and Finnish Children","volume":"7","author":"Kumbhare","year":"2017","journal-title":"Sci. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1002\/humu.23769","article-title":"A2ML1 and Otitis Media: Novel Variants, Differential Expression, and Relevant Pathways","volume":"40","author":"Larson","year":"2019","journal-title":"Hum. Mutat."},{"key":"B34","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) Project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat. Genet."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data With Deseq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/srep25575","article-title":"Muc5ac Gastric Mucin Glycosylation is Shaped by FUT2 Activity and Functionally Impacts Helicobacter Pylori Binding","volume":"6","author":"Magalhaes","year":"2016","journal-title":"Sci. Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1002\/jcp.1041040207","article-title":"Variant Endothelial Cells. Fibronectin as a Transducer of Signals for Migration and Neovascularisation","volume":"104","author":"McAuslan","year":"1980","journal-title":"J. Cell Physiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1083\/jcb.92.2.485","article-title":"Role of Fibronectin in Collagen Deposition: Fab\u2019 to the Gelatin-Binding Domain of Fibronectin Inhibits Both Fibronectin and Collagen Organization in Fibroblast Extracellular Matrix","volume":"92","author":"McDonald","year":"1982","journal-title":"J. Cell Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"7796","DOI":"10.1074\/jbc.RA118.002250","article-title":"Surface-Exposed Loops and an Acidic Patch in the Scl1 Protein of Group A Streptococcus Enable Scl1 Binding to Wound-Associated Fibronectin","volume":"293","author":"McNitt","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"D419","DOI":"10.1093\/nar\/gky1038","article-title":"PANTHER Version 14: More Genomes, a New PANTHER GO-Slim and Improvements in Enrichment Analysis Tools","volume":"47","author":"Mi","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.jgg.2014.10.003","article-title":"Immunity Genes and Susceptibility to Otitis Media: A Comprehensive Review","volume":"41","author":"Mittal","year":"2014","journal-title":"J. Genet. Genomics"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e36226","DOI":"10.1371\/journal.pone.0036226","article-title":"Burden of Disease Caused by Otitis Media: Systematic Review and Global Estimates","volume":"7","author":"Monasta","year":"2012","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/ng.646","article-title":"Exome Sequencing Identifies MLL2 Mutations as a Cause of Kabuki Syndrome","volume":"42","author":"Ng","year":"2010","journal-title":"Nat. Genet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1542\/peds.99.3.318","article-title":"Otitis Media in 2253 Pittsburgh-Area Infants: Prevalence and Risk Factors During the First Two Years of Life","volume":"99","author":"Paradise","year":"1997","journal-title":"Pediatrics"},{"key":"B45","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/ng.3570","article-title":"Detection and Interpretation of Shared Genetic Influences on 42 Human Traits","volume":"48","author":"Pickrell","year":"2016","journal-title":"Nat. Genet."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1093\/bioinformatics\/bts252","article-title":"SINA: Accurate High-Throughput Multiple Sequence Alignment of Ribosomal RNA Genes","volume":"28","author":"Pruesse","year":"2012","journal-title":"Bioinformatics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"L576","DOI":"10.1152\/ajplung.00127.2021","article-title":"Paramyxovirus Replication Induces the Hexosamine Biosynthetic Pathway and Mesenchymal Transition via the IRE1alpha-XBP1s Arm of the Unfolded Protein Response","volume":"321","author":"Qiao","year":"2021","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA Ribosomal RNA Gene Database Project: Improved Data Processing and Web-Based Tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"19030","DOI":"10.1073\/pnas.1106408108","article-title":"Colonic Mucosa-Associated Microbiota is Influenced by an Interaction of Crohn Disease and FUT2 (Secretor) Genotype","volume":"108","author":"Rausch","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B50","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1093\/bioinformatics\/btt526","article-title":"Explicet: Graphical User Interface Software for Metadata-Driven Management, Analysis and Visualization of Microbiome Data","volume":"29","author":"Robertson","year":"2013","journal-title":"Bioinformatics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1177\/0194599813487302","article-title":"Clinical Practice Guideline: Tympanostomy Tubes in Children","volume":"149","author":"Rosenfeld","year":"2013","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"B52","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1177\/0194599815623467","article-title":"Clinical Practice Guideline: Otitis Media With Effusion (Update)","volume":"154","author":"Rosenfeld","year":"2016","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00358","article-title":"Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection","volume":"11","author":"Ryan","year":"2020","journal-title":"Front. Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.ajhg.2018.09.010","article-title":"FUT2 Variants Confer Susceptibility to Familial Otitis Media","volume":"103","author":"Santos-Cortez","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"B55","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.3192","article-title":"Spatial Reconstruction of Single-Cell Gene Expression Data","volume":"33","author":"Satija","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"16063","DOI":"10.1038\/nrdp.2016.63","article-title":"Otitis Media","volume":"2","author":"Schilder","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B57","doi-asserted-by":"publisher","first-page":"4511","DOI":"10.1021\/acs.jproteome.5b00196","article-title":"Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce More Profound Proteomic Host Responses Than Seasonal and Pandemic H1N1 Strains","volume":"14","author":"Simon","year":"2015","journal-title":"J. Proteome Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1016\/j.ijporl.2013.08.012","article-title":"Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Micro Particle","volume":"77","author":"Song","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1002\/lary.29551","article-title":"RNA Sequencing and Pathways Analyses of Middle Ear Epithelia From Patients With Otitis Media","volume":"131","author":"Stabenau","year":"2021","journal-title":"Laryngoscope"},{"key":"B60","doi-asserted-by":"publisher","first-page":"7479","DOI":"10.1016\/j.vaccine.2018.10.060","article-title":"Acute Otitis Media, Antimicrobial Prescriptions, and Medical Expenses Among Children in the United States During 2011-2016","volume":"36","author":"Suaya","year":"2018","journal-title":"Vaccine"},{"key":"B61","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/s41467-017-00257-5","article-title":"Genome-Wide Association and HLA Region Fine-Mapping Studies Identify Susceptibility Loci for Multiple Common Infections","volume":"8","author":"Tian","year":"2017","journal-title":"Nat. Commun."},{"key":"B62","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1080\/19490976.2018.1445956","article-title":"FUT2 Genotype and Secretory Status are Not Associated With Fecal Microbial Composition and Inferred Function in Healthy Subjects","volume":"9","author":"Turpin","year":"2018","journal-title":"Gut. Microbes"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-Based Map of the Human Proteome","volume":"347","author":"Uhlen","year":"2015","journal-title":"Science"},{"key":"B64","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1093\/molbev\/msi222","article-title":"A Novel Gene Family NBPF: Intricate Structure Generated by Gene Duplications During Primate Evolution","volume":"22","author":"Vandepoele","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"e20113","DOI":"10.1371\/journal.pone.0020113","article-title":"Secretor Genotype (FUT2 Gene) is Strongly Associated With the Composition of Bifidobacteria in the Human Intestine","volume":"6","author":"Wacklin","year":"2011","journal-title":"PLoS One"},{"key":"B66","doi-asserted-by":"publisher","first-page":"e94863","DOI":"10.1371\/journal.pone.0094863","article-title":"Faecal Microbiota Composition in Adults is Associated With the FUT2 Gene Determining the Secretor Status","volume":"9","author":"Wacklin","year":"2014","journal-title":"PLoS One"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1002\/ajmg.a.31724","article-title":"Methylthioadenosine Phosphorylase (MTAP) in Hearing: Gene Disruption by Chromosomal Rearrangement in a Hearing Impaired Individual and Model Organism Analysis","author":"Williamson","year":"2007","journal-title":"Am. J. Med. Genet. A."},{"key":"B68","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1002\/j.1460-2075.1986.tb04265.x","article-title":"Adhesion and Cytoskeletal Organisation of Fibroblasts in Response to Fibronectin Fragments","volume":"5","author":"Woods","year":"1986","journal-title":"EMBO J."},{"key":"B69","doi-asserted-by":"publisher","first-page":"W167","DOI":"10.1093\/nar\/gku443","article-title":"NetworkAnalyst\u2013integrative Approaches for Protein-Protein Interaction Network Analysis and Visual Exploration","volume":"42","author":"Xia","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B70","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/nprot.2015.052","article-title":"NetworkAnalyst for Statistical, Visual and Network-Based Meta-Analysis of Gene Expression Data","volume":"10","author":"Xia","year":"2015","journal-title":"Nat. Protoc."},{"key":"B71","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.ydbio.2009.02.033","article-title":"Rasip1 is Required for Endothelial Cell Motility, Angiogenesis and Vessel Formation","volume":"329","author":"Xu","year":"2009","journal-title":"Dev. Biol."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2021.110629","article-title":"Nasopharyngeal Microbiome Analyses in Otitis-Prone and Otitis-Free Children","volume":"143","author":"Xu","year":"2021","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.devcel.2011.02.010","article-title":"Blood Vessel Tubulogenesis Requires Rasip1 Regulation of GTPase Signaling","volume":"20","author":"Xu","year":"2011","journal-title":"Dev. Cell"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.144360","article-title":"Identification of KMT2D and KDM6A Variants by Targeted Sequencing From Patients With Kabuki Syndrome and Other Congenital Disorders","volume":"731","author":"Yap","year":"2020","journal-title":"Gene"},{"key":"B75","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.diagmicrobio.2016.02.010","article-title":"Detection of Respiratory Pathogens in Pediatric Acute Otitis Media by PCR and Comparison of Findings in the Middle Ear and Nasopharynx","volume":"85","author":"Yatsyshina","year":"2016","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"B76","doi-asserted-by":"publisher","first-page":"e86397","DOI":"10.1371\/journal.pone.0086397","article-title":"Risk Factors for Chronic and Recurrent Otitis Media-a Meta-Analysis","volume":"9","author":"Zhang","year":"2014","journal-title":"PLoS One"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.798246\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:59:38Z","timestamp":1642139978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.798246\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,14]]},"references-count":76,"alternative-id":["10.3389\/fcimb.2021.798246"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.798246","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,14]]},"article-number":"798246"}}