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Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination.<\/jats:p>","DOI":"10.1073\/pnas.1822046116","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T19:49:02Z","timestamp":1565380142000},"page":"17121-17126","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination"],"prefix":"10.1073","volume":"116","author":[{"given":"Di\u00f3genes S.","family":"de Lima","sequence":"first","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, 05508-000 S\u00e3o Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas E.","family":"Cardozo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, 05508-000 S\u00e3o Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius","family":"Maracaja-Coutinho","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, 8380492 Santiago, Chile;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Suhrbier","sequence":"additional","affiliation":[{"name":"Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Mane","sequence":"additional","affiliation":[{"name":"Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia at LSHTM, Banjul, The Gambia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jeffries","sequence":"additional","affiliation":[{"name":"Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia at LSHTM, Banjul, The Gambia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo L. 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Johnson, Long non-coding RNAs in Huntington\u2019s disease neurodegeneration. Neurobiol. Dis. 46, 245\u2013254 (2012).","journal-title":"Neurobiol. Dis."},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2012.06.004","article-title":"Long non-coding RNA expression profiles predict clinical phenotypes in glioma","volume":"48","author":"Zhang X.","year":"2012","unstructured":"X. Zhang ., Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol. Dis. 48, 1\u20138 (2012).","journal-title":"Neurobiol. Dis."},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/ni.2789","article-title":"Molecular signatures of antibody responses derived from a systems biology study of five human vaccines","volume":"15","author":"Li S.","year":"2014","unstructured":"S. Li ., Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat. Immunol. 15, 195\u2013204 (2014).","journal-title":"Nat. Immunol."},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer W.","year":"2010","unstructured":"W. Viechtbauer, Conducting meta-analyses in R with the metafor package. J. Stat. Softw. 36, 1\u201348 (2010).","journal-title":"J. Stat. Softw."},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nbt.2153","article-title":"BLUEPRINT to decode the epigenetic signature written in blood","volume":"30","author":"Adams D.","year":"2012","unstructured":"D. Adams ., BLUEPRINT to decode the epigenetic signature written in blood. Nat. Biotechnol. 30, 224\u2013226 (2012).","journal-title":"Nat. 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Trends Genet. 32, 620\u2013637 (2016).","journal-title":"Trends Genet."},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12859-018-2053-1","article-title":"CEMiTool: A Bioconductor package for performing comprehensive modular co-expression analyses","volume":"19","author":"Russo P. S. T.","year":"2018","unstructured":"P. S. T. Russo ., CEMiTool: A Bioconductor package for performing comprehensive modular co-expression analyses. BMC Bioinf. 19, 56 (2018).","journal-title":"BMC Bioinf."},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"016110","DOI":"10.1103\/PhysRevE.74.016110","article-title":"Statistical mechanics of community detection","volume":"74","author":"Reichardt J.","year":"2006","unstructured":"J. Reichardt, S. Bornholdt, Statistical mechanics of community detection. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 74, 016110 (2006).","journal-title":"Phys. Rev. E Stat. Nonlin. Soft Matter Phys."},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s10038-006-0070-9","article-title":"Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction","volume":"51","author":"Ishii N.","year":"2006","unstructured":"N. Ishii ., Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J. Hum. Genet. 51, 1087\u20131099 (2006).","journal-title":"J. Hum. Genet."},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12929-018-0427-3","article-title":"Long non-coding RNA MIAT in development and disease: A new player in an old game","volume":"25","author":"Sun C.","year":"2018","unstructured":"C. Sun ., Long non-coding RNA MIAT in development and disease: A new player in an old game. J. Biomed. Sci. 25, 23 (2018).","journal-title":"J. Biomed. 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Kopp, J. T. Mendell, Functional classification and experimental dissection of long noncoding RNAs. Cell 172, 393\u2013407 (2018).","journal-title":"Cell"},{"key":"e_1_3_4_54_2","first-page":"656","article-title":"BLAT\u2013The BLAST-like alignment tool","volume":"12","author":"Kent W. J.","year":"2002","unstructured":"W. J. Kent, BLAT\u2013The BLAST-like alignment tool. Genome Res. 12, 656\u2013664 (2002).","journal-title":"Genome Res."},{"key":"e_1_3_4_55_2","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: A flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan A. R.","year":"2010","unstructured":"A. R. Quinlan, I. M. Hall, BEDTools: A flexible suite of utilities for comparing genomic features. 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Ritchie ., limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_4_59_2","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy D. J.","year":"2012","unstructured":"D. J. McCarthy, Y. Chen, G. K. Smyth, Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 40, 4288\u20134297 (2012).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_4_60_2","doi-asserted-by":"crossref","first-page":"e1003118","DOI":"10.1371\/journal.pcbi.1003118","article-title":"Software for computing and annotating genomic ranges","volume":"9","author":"Lawrence M.","year":"2013","unstructured":"M. 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