{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T02:57:19Z","timestamp":1776913039058,"version":"3.51.2"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T00:00:00Z","timestamp":1459987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T00:00:00Z","timestamp":1459987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genes Immun"],"published-print":{"date-parts":[[2016,6]]},"DOI":"10.1038\/gene.2016.15","type":"journal-article","created":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T09:05:22Z","timestamp":1460019922000},"page":"244-250","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["An interaction quantitative trait loci tool implicates epistatic functional variants in an apoptosis pathway in smallpox vaccine eQTL data"],"prefix":"10.1038","volume":"17","author":[{"given":"C A","family":"Lareau","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B C","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A L","family":"Oberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R B","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G A","family":"Poland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B A","family":"McKinney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,4,7]]},"reference":[{"key":"BFgene201615_CR1","doi-asserted-by":"publisher","first-page":"e1002197","DOI":"10.1371\/journal.pgen.1002197","volume":"7","author":"RS Fehrmann","year":"2011","unstructured":"Fehrmann RS, Jansen RC, Veldink JH, Westra HJ, Arends D, Bonder MJ et al. Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA. PLoS Genet 2011; 7: e1002197.","journal-title":"PLoS Genet"},{"key":"BFgene201615_CR2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/ejhg.2011.156","volume":"20","author":"J Becker","year":"2012","unstructured":"Becker J, Wendland JR, Haenisch B, Nothen MM, Schumacher J . A systematic eQTL study of cis-trans epistasis in 210 HapMap individuals. Eur J Hum Genet 2012; 20: 97\u2013101.","journal-title":"Eur J Hum Genet"},{"key":"BFgene201615_CR3","doi-asserted-by":"publisher","first-page":"e28415","DOI":"10.1371\/journal.pone.0028415","volume":"6","author":"K Kapur","year":"2011","unstructured":"Kapur K, Schupbach T, Xenarios I, Kutalik Z, Bergmann S . Comparison of strategies to detect epistasis from eQTL data. PLoS One 2011; 6: e28415.","journal-title":"PLoS One"},{"key":"BFgene201615_CR4","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1093\/hmg\/11.20.2463","volume":"11","author":"HJ Cordell","year":"2002","unstructured":"Cordell HJ . Epistasis: what it means, what it doesn\u2019t mean, and statistical methods to detect it in humans. Hum Mol Genet 2002; 11: 2463\u20132468.","journal-title":"Hum Mol Genet"},{"key":"BFgene201615_CR5","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/nrg2452","volume":"9","author":"PC Phillips","year":"2008","unstructured":"Phillips PC . Epistasis\u2014the essential role of gene interactions in the structure and evolution of genetic systems. Nat Rev Genet 2008; 9: 855\u2013867.","journal-title":"Nat Rev Genet"},{"key":"BFgene201615_CR6","doi-asserted-by":"publisher","first-page":"e1002912","DOI":"10.1371\/journal.pgen.1002912","volume":"8","author":"G Liti","year":"2012","unstructured":"Liti G, Louis EJ . Advances in quantitative trait analysis in yeast. PLoS Genet 2012; 8: e1002912.","journal-title":"PLoS Genet"},{"key":"BFgene201615_CR7","doi-asserted-by":"publisher","first-page":"e1003321","DOI":"10.1371\/journal.pgen.1003321","volume":"9","author":"L Ma","year":"2013","unstructured":"Ma L, Clark AG, Keinan A . Gene-based testing of interactions in association studies of quantitative traits. PLoS Genet 2013; 9: e1003321.","journal-title":"PLoS Genet"},{"key":"BFgene201615_CR8","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1073\/pnas.1119675109","volume":"109","author":"O Zuk","year":"2012","unstructured":"Zuk O, Hechter E, Sunyaev SR, Lander ES . The mystery of missing heritability: genetic interactions create phantom heritability. Proc Natl Acad Sci USA 2012; 109: 1193\u20131198.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFgene201615_CR9","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559\u2013575.","journal-title":"Am J Hum Genet"},{"key":"BFgene201615_CR10","doi-asserted-by":"publisher","first-page":"5262","DOI":"10.1016\/j.vaccine.2015.04.088","volume":"33","author":"AL Oberg","year":"2015","unstructured":"Oberg AL, McKinney BA, Schaid DJ, Pankratz VS, Kennedy RB, Poland GA . Lessons learned in the analysis of high-dimensional data in vaccinomics. Vaccine 2015; 33: 5262\u20135270.","journal-title":"Vaccine"},{"key":"BFgene201615_CR11","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/msb.2013.15","volume":"9","author":"D Furman","year":"2013","unstructured":"Furman D, Jojic V, Kidd B, Shen-Orr S, Price J, Jarrell J et al. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness. Mol Syst Biol 2013; 9: 659.","journal-title":"Mol Syst Biol"},{"key":"BFgene201615_CR12","doi-asserted-by":"publisher","first-page":"W484","DOI":"10.1093\/nar\/gks458","volume":"40","author":"AK Wong","year":"2012","unstructured":"Wong AK, Park CY, Greene CS, Bongo LA, Guan Y, Troyanskaya OG . IMP: a multi-species functional genomics portal for integration, visualization and prediction of protein functions and networks. Nucleic Acids Res 2012; 40: W484\u2013W490.","journal-title":"Nucleic Acids Res"},{"key":"BFgene201615_CR13","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nrg2579","volume":"10","author":"HJ Cordell","year":"2009","unstructured":"Cordell HJ . Detecting gene-gene interactions that underlie human diseases. Nat Rev Genet 2009; 10: 392\u2013404.","journal-title":"Nat Rev Genet"},{"key":"BFgene201615_CR14","first-page":"51","volume":"4","author":"Y Huang","year":"2013","unstructured":"Huang Y, Wuchty S, Przytycka TM . eQTL epistasis\u2014challenges and computational approaches. Front Genet 2013; 4: 51.","journal-title":"Front Genet"},{"key":"BFgene201615_CR15","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1002\/gepi.21739","volume":"37","author":"NA Davis","year":"2013","unstructured":"Davis NA, Lareau CA, White BC, Pandey A, Wiley G, Montgomery CG et al. Encore: Genetic Association Interaction Network centrality pipeline and application to SLE exome data. Genet Epidemiol 2013; 37: 614\u2013621.","journal-title":"Genet Epidemiol"},{"key":"BFgene201615_CR16","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13040-015-0040-x","volume":"8","author":"CA Lareau","year":"2015","unstructured":"Lareau CA, White BC, Oberg AL, McKinney BA . Differential co-expression network centrality and machine learning feature selection for identifying susceptibility hubs in networks with scale-free structure. BioData Min 2015; 8: 5.","journal-title":"BioData Min"},{"key":"BFgene201615_CR17","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/gene.2010.37","volume":"11","author":"NA Davis","year":"2010","unstructured":"Davis NA, Crowe Jr JE, Pajewski NM, McKinney BA . Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine. Genes Immun 2010; 11: 630\u2013636.","journal-title":"Genes Immun"},{"key":"BFgene201615_CR18","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.smim.2013.04.007","volume":"25","author":"GA Poland","year":"2013","unstructured":"Poland GA, Kennedy RB, McKinney BA, Ovsyannikova IG, Lambert ND, Jacobson RM et al. Vaccinomics, adversomics, and the immune response network theory: individualized vaccinology in the 21st century. Semin Immunol 2013; 25: 89\u2013103.","journal-title":"Semin Immunol"},{"key":"BFgene201615_CR19","doi-asserted-by":"publisher","first-page":"e81527","DOI":"10.1371\/journal.pone.0081527","volume":"8","author":"BA McKinney","year":"2013","unstructured":"McKinney BA, White BC, Grill DE, Li PW, Kennedy RB, Poland GA et al. ReliefSeq: a gene-wise adaptive-K nearest-neighbor feature selection tool for finding gene\u2013gene interactions and main effects in mRNA-Seq gene expression data. PLoS One 2013; 8: e81527.","journal-title":"PLoS One"},{"key":"BFgene201615_CR20","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0092-8674(00)00009-X","volume":"102","author":"AM Verhagen","year":"2000","unstructured":"Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000; 102: 43\u201353.","journal-title":"Cell"},{"key":"BFgene201615_CR21","doi-asserted-by":"publisher","first-page":"e23262","DOI":"10.1371\/journal.pone.0023262","volume":"6","author":"SL Zhao","year":"2011","unstructured":"Zhao SL, Hong J, Xie ZQ, Tang JT, Su WY, Du W et al. TRAPPC4-ERK2 interaction activates ERK1\/2, modulates its nuclear localization and regulates proliferation and apoptosis of colorectal cancer cells. PLoS One 2011; 6: e23262.","journal-title":"PLoS One"},{"key":"BFgene201615_CR22","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/0092-8674(95)90071-3","volume":"81","author":"AM Chinnaiyan","year":"1995","unstructured":"Chinnaiyan AM, O\u2019Rourke K, Tewari M, Dixit VM . FADD a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 1995; 81: 505\u2013512.","journal-title":"Cell"},{"key":"BFgene201615_CR23","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1002\/bies.1062","volume":"23","author":"CI Smith","year":"2001","unstructured":"Smith CI, Islam TC, Mattsson PT, Mohamed AJ, Nore BF, Vihinen M . The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. BioEssays 2001; 23: 436\u2013446.","journal-title":"BioEssays"},{"key":"BFgene201615_CR24","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/emm.2007.86","volume":"39","author":"B Choi","year":"2007","unstructured":"Choi B, Suh Y, Kim WH, Christa L, Park J, Bae CD . Downregulation of regenerating islet-derived 3 alpha (REG3A) in primary human gastric adenocarcinomas. Exp Mol Med 2007; 39: 796\u2013804.","journal-title":"Exp Mol Med"},{"key":"BFgene201615_CR25","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S0952-7915(00)00148-5","volume":"12","author":"NP Restifo","year":"2000","unstructured":"Restifo NP . Building better vaccines: how apoptotic cell death can induce inflammation and activate innate and adaptive immunity. Curr Opin Immunol 2000; 12: 597\u2013603.","journal-title":"Curr Opin Immunol"},{"key":"BFgene201615_CR26","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1084\/jem.191.3.475","volume":"191","author":"KG Smith","year":"2000","unstructured":"Smith KG, Light A, O\u2019Reilly LA, Ang SM, Strasser A, Tarlinton D . Bcl-2 transgene expression inhibits apoptosis in the germinal center and reveals differences in the selection of memory B cells and bone marrow antibody-forming cells. J Exp Med 2000; 191: 475\u2013484.","journal-title":"J Exp Med"},{"key":"BFgene201615_CR27","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1084\/jem.182.1.129","volume":"182","author":"T Zhou","year":"1995","unstructured":"Zhou T, Edwards CK, Mountz JD . Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice. J Exp Med 1995; 182: 129\u2013137.","journal-title":"J Exp Med"},{"key":"BFgene201615_CR28","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/ijc.10777","volume":"103","author":"SR Scheffer","year":"2003","unstructured":"Scheffer SR, Nave H, Korangy F, Schlote K, Pabst R, Jaffee EM et al. Apoptotic, but not necrotic, tumor cell vaccines induce a potent immune response in vivo. Int J Cancer 2003; 103: 205\u2013211.","journal-title":"Int J Cancer"},{"key":"BFgene201615_CR29","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12985-015-0241-4","volume":"12","author":"MH Lehman","year":"2015","unstructured":"Lehman MH, Price PJ, Brandmuller C, Sutter G . Modified Vaccinia virus Ankara but not vaccinia virus induces chemokine expression in cells of the monocyte\/macrophage lineage. Virol J 2015; 12: 12\u201321.","journal-title":"Virol J"},{"key":"BFgene201615_CR30","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1471-2172-9-15","volume":"9","author":"L Liu","year":"2008","unstructured":"Liu L, Chavan R, Feinberg MB . Dendritic cells are preferentially targeted among hematolymphocytes by Modified Vaccinia Virus Ankara and play a key role in the induction of virus-specific T cell responses in vivo. BMC Immunol 2008; 9: 15.","journal-title":"BMC Immunol"},{"key":"BFgene201615_CR31","unstructured":"OpenMP. Application Program Interface, 2008. Available at: http:\/\/www.openmp.org\/mp-documents\/spec30.pdf accesed 22 March 2016."},{"key":"BFgene201615_CR32","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1093\/infdis\/jis546","volume":"206","author":"IH Haralambieva","year":"2012","unstructured":"Haralambieva IH, Oberg AL, Dhiman N, Ovsyannikova IG, Kennedy RB, Grill DE et al. High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination. J Infect Dis 2012; 206: 1512\u20131520.","journal-title":"J Infect Dis"},{"key":"BFgene201615_CR33","doi-asserted-by":"publisher","first-page":"3319","DOI":"10.1016\/j.vaccine.2009.01.086","volume":"27","author":"RB Kennedy","year":"2009","unstructured":"Kennedy RB, Ovsyannikova IG, Pankratz VS, Vierkant RA, Jacobson RM, Ryan MA et al. Gender effects on humoral immune responses to smallpox vaccine. Vaccine 2009; 27: 3319\u20133323.","journal-title":"Vaccine"},{"key":"BFgene201615_CR34","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1093\/infdis\/jir268","volume":"204","author":"IH Haralambieva","year":"2011","unstructured":"Haralambieva IH, Ovsyannikova IG, Dhiman N, Kennedy RB, O\u2019Byrne M, Pankratz VS et al. Common SNPs\/haplotypes in IL18R1 and IL18 genes are associated with variations in humoral immunity to smallpox vaccination in Caucasians and African Americans. J Infect Dis 2011; 204: 433\u2013441.","journal-title":"J Infect Dis"},{"key":"BFgene201615_CR35","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1089\/vim.2011.0029","volume":"24","author":"BJ Umlauf","year":"2011","unstructured":"Umlauf BJ, Ovsyannikova IG, Haralambieva IH, Kennedy RB, Vierkant RA, Pankratz VS et al. Correlations between vaccinia-specific immune responses within a cohort of armed forces members. Viral Immunol 2011; 24: 415\u2013420.","journal-title":"Viral Immunol"},{"key":"BFgene201615_CR36","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jim.2011.01.011","volume":"366","author":"AL Oberg","year":"2011","unstructured":"Oberg AL, Dhiman N, Grill DE, Ryan JE, Kennedy RB, Poland GA . Optimizing high dimensional gene expression studies for immune response following smallpox vaccination using Taqman(R) low density immune arrays. J Immunol Methods 2011; 366: 69\u201378.","journal-title":"J Immunol Methods"},{"key":"BFgene201615_CR37","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1007\/s00439-012-1179-x","volume":"131","author":"RB Kennedy","year":"2012","unstructured":"Kennedy RB, Ovsyannikova IG, Pankratz VS, Haralambieva IH, Vierkant RA, Jacobson RM et al. Genome-wide genetic associations with IFNgamma response to smallpox vaccine. Hum Genet 2012; 131: 1433\u20131451.","journal-title":"Hum Genet"},{"key":"BFgene201615_CR38","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/s12026-014-8516-1","volume":"58","author":"S Bhattacharya","year":"2014","unstructured":"Bhattacharya S, Andorf S, Gomes L, Dunn P, Schaefer H, Pontius J et al. ImmPort: disseminating data to the public for the future of immunology. Immunol Res 2014; 58: 234\u2013239.","journal-title":"Immunol Res"},{"key":"BFgene201615_CR39","doi-asserted-by":"crossref","unstructured":"Turner SD, Bush WS . Multivariate analysis of regulatory SNPs: empowering personal genomics by considering cis-epistasis and heterogeneity. Pac Symp Biocomput 2011: 276\u2013287.","DOI":"10.1142\/9789814335058_0029"},{"key":"BFgene201615_CR40","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/978-1-4939-2155-3_15","volume":"1253","author":"CA Lareau","year":"2015","unstructured":"Lareau CA, McKinney BA . Network theory for data-driven epistasis networks. Methods Mol Biol 2015; 1253: 285\u2013300.","journal-title":"Methods Mol Biol"},{"key":"BFgene201615_CR41","doi-asserted-by":"publisher","first-page":"312","DOI":"10.3389\/fgene.2015.00312","volume":"6","author":"CA Lareau","year":"2015","unstructured":"Lareau CA, White BC, Montgomery C, McKinney BA . dcVar: a method for identifying common variants that modulate differential correlation structures in gene expression data. Front Genet 2015; 6: 312.","journal-title":"Front Genet"},{"key":"BFgene201615_CR42","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/gepi.21754","volume":"37","author":"Y Wu","year":"2013","unstructured":"Wu Y, Zhu X, Chen J, Zhang X . EINVis: a visualization tool for analyzing and exploring genetic interactions in large-scale association studies. Genet Epidemiol 2013; 37: 675\u2013685.","journal-title":"Genet Epidemiol"}],"container-title":["Genes &amp; Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/gene201615.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gene201615","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gene201615.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T04:49:09Z","timestamp":1744174149000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/gene201615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,7]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["BFgene201615"],"URL":"https:\/\/doi.org\/10.1038\/gene.2016.15","relation":{},"ISSN":["1466-4879","1476-5470"],"issn-type":[{"value":"1466-4879","type":"print"},{"value":"1476-5470","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,7]]},"assertion":[{"value":"5 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr Poland offers consultative advice on vaccine development to Merck & Co. Inc., CSL Biotherapies, Avianax, Dynavax, Novartis Vaccines and Therapeutics, Emergent Biosolutions, Adjuvance and Microdermis. Dr Poland holds two patents related to vaccinia and measles peptide research. These research activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}