{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T13:10:00Z","timestamp":1779023400221,"version":"3.51.4"},"reference-count":24,"publisher":"American Association for the Advancement of Science (AAAS)","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":315,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007911","name":"University of California, San Diego","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007911","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012424","name":"University of California San Diego School of Medicine","doi-asserted-by":"publisher","award":["RG096559"],"award-info":[{"award-number":["RG096559"]}],"id":[{"id":"10.13039\/100012424","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012424","name":"University of California San Diego School of Medicine","doi-asserted-by":"publisher","award":["RG096651"],"award-info":[{"award-number":["RG096651"]}],"id":[{"id":"10.13039\/100012424","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["csbj.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Comput Struct Biotechnol J"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The mechanisms of carcinogenesis from viral infections are extraordinarily complex and not well understood. Traditional methods of analyzing RNA-sequencing data may not be sufficient for unraveling complicated interactions between viruses and host cells. Using RNA and DNA-sequencing data from The Cancer Genome Atlas (TCGA), we aim to explore whether virus-induced tumors exhibit similar immune-associated (IA) dysregulations using a new algorithm we developed that focuses on the most important biological mechanisms involved in virus-induced cancers. Differential expression, survival correlation, and clinical variable correlations were used to identify the most clinically relevant IA genes dysregulated in 5 virus-induced cancers (HPV-induced head and neck squamous cell carcinoma, HPV-induced cervical cancer, EBV-induced stomach cancer, HBV-induced liver cancer, and HCV-induced liver cancer) after which a mechanistic approach was adopted to identify pathways implicated in IA gene dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results revealed that IA dysregulations vary with the cancer type and the virus type, but cytokine signaling pathways are dysregulated in all virus-induced cancers. Furthermore, we also found that important similarities exist between all 5 virus-induced cancers in dysregulated clinically relevant oncogenic signatures and IA pathways. Finally, we also discovered potential mechanisms for genomic alterations to induce IA gene dysregulations using our algorithm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study offers a new approach to mechanism identification through integrating functional annotations and large-scale sequencing data, which may be invaluable to the discovery of new immunotherapy targets for virus-induced cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.csbj.2021.11.013","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T21:39:17Z","timestamp":1637185157000},"page":"6240-6254","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach"],"prefix":"10.34133","volume":"19","author":[{"given":"Lindsay M.","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Tse","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Shende","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph C.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaideep","family":"Chakladar","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditi","family":"Gnanasekar","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanhao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kypros","family":"Dereschuk","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Wang-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Pathology Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weg M.","family":"Ongkeko","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2007.12.005"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1659743"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6104047"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s12859-017-1571-6","article-title":"Avoiding the pitfalls of gene set enrichment analysis with SetRank","volume":"18","author":"Simillion C.","year":"2017","unstructured":"Simillion C., Liechti R., Lischer H.E.L., Ioannidis V. and Bruggmann R.: Avoiding the pitfalls of gene set enrichment analysis with SetRank. BMC Bioinf 2017; 18: 151.","journal-title":"BMC Bioinf"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0103-9"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/0962280212460441"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1186\/1471-2164-11-574","article-title":"Heading down the wrong pathway: on the influence of correlation within gene sets","volume":"11","author":"Gatti D.M.","year":"2010","unstructured":"Gatti D.M. et al: Heading down the wrong pathway: on the influence of correlation within gene sets. BMC Genomics 2010; 11: 574.","journal-title":"BMC Genomics"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.003"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.1158\/0008-5472.CAN-08-1178","article-title":"EBV latent membrane protein 1 effects on plakoglobin, cell growth, and migration","volume":"68","author":"Shair K.H.Y.","year":"2008","unstructured":"Shair K.H.Y., Schnegg C.I. and Raab-Traub N.: EBV latent membrane protein 1 effects on plakoglobin, cell growth, and migration. Cancer Res 2008; 68: 6997.","journal-title":"Cancer Res"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/v4123420"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"534","DOI":"10.2174\/1568009616666160926124923","article-title":"Epstein-Barr virus-associated gastric cancer and potential mechanisms of oncogenesis","volume":"17","author":"Morales-Sanchez A.","year":"2017","unstructured":"Morales-Sanchez A. and Fuentes-Panana E.M.: Epstein-Barr virus-associated gastric cancer and potential mechanisms of oncogenesis. Curr Cancer Drug Targets 2017; 17: 534.","journal-title":"Curr Cancer Drug Targets"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11262-009-0412-8","article-title":"The biological properties of E6 and E7 oncoproteins from human papillomaviruses","volume":"40","author":"Ghittoni R.","year":"2010","unstructured":"Ghittoni R., Accardi R., Hasan U., Gheit T., Sylla B. and Tommasino M.: The biological properties of E6 and E7 oncoproteins from human papillomaviruses. Virus Genes 2010; 40: 1.","journal-title":"Virus Genes"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.ygyno.2013.08.025","article-title":"Immune responses against virus and tumor in cervical carcinogenesis: treatment strategies for avoiding the HPV-induced immune escape","volume":"131","author":"Conesa-Zamora P.","year":"2013","unstructured":"Conesa-Zamora P.: Immune responses against virus and tumor in cervical carcinogenesis: treatment strategies for avoiding the HPV-induced immune escape. Gynecol Oncol 2013; 131: 480.","journal-title":"Gynecol Oncol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"11630","DOI":"10.3748\/wjg.v20.i33.11630","article-title":"Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis","volume":"20","author":"Tarocchi M.","year":"2014","unstructured":"Tarocchi M. et al: Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis. World J Gastroenterol 2014; 20: 11630.","journal-title":"World J Gastroenterol"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2016.01.022"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.7150\/jca.13150","article-title":"Genome-wide analysis of Epstein-Barr virus (EBV) integration and strain in C666-1 and Raji cells","volume":"7","author":"Xiao K.","year":"2016","unstructured":"Xiao K., Yu Z., Li X., Li X., Tang K., Tu C. et al: Genome-wide analysis of Epstein-Barr virus (EBV) integration and strain in C666-1 and Raji cells. J Cancer 2016; 7: 214.","journal-title":"J Cancer"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.05.023"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","unstructured":"Samuel CE Antiviral actions of interferons. Clin Microbiol Rev 2001: 14(4); 778-809 table of contents.","DOI":"10.1128\/CMR.14.4.778-809.2001"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S1074-7613(01)00154-6","article-title":"Interferons alpha and beta as immune regulators\u2013a new look","volume":"14","author":"Biron C.A.","year":"2001","unstructured":"Biron C.A.: Interferons alpha and beta as immune regulators\u2013a new look. Immunity 2001; 14: 661.","journal-title":"Immunity"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-014-8516-1"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2008.55"},{"key":"e_1_3_4_24_2","first-page":"146","article-title":"ReactomeFIViz: a Cytoscape app for pathway and network-based data analysis","volume":"3","author":"Wu G.","year":"2014","unstructured":"Wu G. et al: ReactomeFIViz: a Cytoscape app for pathway and network-based data analysis. F1000Research 2014; 3: 146.","journal-title":"F1000Research"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"}],"container-title":["Computational and Structural Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2001037021004785?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2001037021004785?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.1016\/j.csbj.2021.11.013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T12:50:50Z","timestamp":1779022250000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.1016\/j.csbj.2021.11.013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":24,"alternative-id":["10.1016\/j.csbj.2021.11.013"],"URL":"https:\/\/doi.org\/10.1016\/j.csbj.2021.11.013","relation":{},"ISSN":["2001-0370"],"issn-type":[{"value":"2001-0370","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Analysis of the immune landscape in virus-induced cancers using a novel integrative mechanism discovery approach","name":"articletitle","label":"Article Title"},{"value":"Computational and Structural Biotechnology Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.csbj.2021.11.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.","name":"copyright","label":"Copyright"}]}}