{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:57:57Z","timestamp":1787997477178,"version":"build-2784847793"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T00:00:00Z","timestamp":1533513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN27220140045C"],"award-info":[{"award-number":["HHSN27220140045C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201200010C"],"award-info":[{"award-number":["HHSN272201200010C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1P01AI106695\u201001A1"],"award-info":[{"award-number":["1P01AI106695\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Epitopes identified in large\u2010scale screens of overlapping peptides often share significant levels of sequence identity, complicating the analysis of epitope\u2010related data. Clustering algorithms are often used to facilitate these analyses, but available methods are generally insufficient in their capacity to define biologically meaningful epitope clusters in the context of the immune response. To fulfil this need we developed an algorithm that generates epitope clusters based on representative or consensus sequences. This tool allows the user to cluster peptide sequences on the basis of a specified level of identity by selecting among three different method options. These include the \u2018clique method\u2019, in which all members of the cluster must share the same minimal level of identity with each other, and the \u2018connected graph method\u2019, in which all members of a cluster must share a defined level of identity with at least one other member of the cluster. In cases where it is not possible to define a clear consensus sequence with the connected graph method, a third option provides a novel \u2018cluster\u2010breaking algorithm\u2019 for consensus sequence driven sub\u2010clustering. Herein we demonstrate the tool's clustering performance and applicability using (i) a selection of dengue virus epitopes for the \u2018clique method\u2019, (ii) sets of allergen\u2010derived peptides from related species for the \u2018connected graph method\u2019 and (iii) large data sets of eluted ligand, major histocompatibility complex binding and T\u2010cell recognition data captured within the Immune Epitope Database (\n                    <jats:styled-content style=\"fixed-case\">IEDB<\/jats:styled-content>\n                    ) with the newly developed \u2018cluster\u2010breaking algorithm\u2019. This novel clustering tool is accessible at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/tools.iedb.org\/cluster2\/\">http:\/\/tools.iedb.org\/cluster2\/<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/imm.12984","type":"journal-article","created":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T03:02:25Z","timestamp":1531796545000},"page":"331-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Development of a novel clustering tool for linear peptide sequences"],"prefix":"10.1111","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1381-7434","authenticated-orcid":false,"given":"Sandeep K.","family":"Dhanda","sequence":"first","affiliation":[{"name":"Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerrie","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Schulten","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2209-5966","authenticated-orcid":false,"given":"Alba","family":"Grifoni","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Weiskopf","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sidney","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjoern","family":"Peters","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla CA USA"},{"name":"Department of Medicine University of California San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery La Jolla Institute for Allergy and Immunology La Jolla CA USA"},{"name":"Department of Medicine University of California San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2007.12.006"},{"key":"e_1_2_8_3_1","first-page":"467","article-title":"Novel in silico tools for designing peptide\u2010based subunit vaccines and immunotherapeutics","volume":"18","author":"Dhanda SK","year":"2017","journal-title":"Brief Bioinform"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.329"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.11.054"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050594"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.3.6.985"},{"key":"e_1_2_8_8_1","first-page":"253","article-title":"HLA\u2010DR restrictive supertypes dominate promiscuous T cell recognition: association of multiple HLA\u2010DR molecules with susceptibility to autoimmune diseases","volume":"24","author":"Ou D","year":"1997","journal-title":"J Rheumatol"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.08.014"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku938"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00278"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty463"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.3"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4161\/self.1.2.11391"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbs197"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22383"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14918"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005760"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"147.13","DOI":"10.4049\/jimmunol.196.Supp.147.13","article-title":"DENV\u2010specific CD4 T\u2010cells dominantly recognize capsid\u2010derived epitopes and display a cytotoxic phenotype","volume":"196","author":"Weiskopf D","year":"2016","journal-title":"J Immunol"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12507"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/763461"},{"key":"e_1_2_8_22_1","first-page":"183","article-title":"Clustering in life sciences","volume":"224","author":"Zhao Y","year":"2003","journal-title":"Methods Mol Biol"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1515\/jib-2016-300"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/bioinformatics\/btv522","article-title":"Hammock: a hidden Markov model\u2010based peptide clustering algorithm to identify protein\u2010interaction consensus motifs in large datasets","volume":"32","author":"Krejci A","year":"2016","journal-title":"Bioinformatics"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr318"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq461"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx248"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts621"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2307\/2786466"},{"key":"e_1_2_8_30_1","volume-title":"Algorithmic Graph Theory","author":"Gibbons A","year":"1985"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-349-03521-2"},{"key":"e_1_2_8_32_1","volume-title":"Introduction to Graph Theory","author":"West DB","year":"2008"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw309"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.02126.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00235"},{"key":"e_1_2_8_36_1","doi-asserted-by":"crossref","unstructured":"AricAH DanielAS PieterJS.Exploring network structure dynamics and function using NetworkX.2008:11\u20135.","DOI":"10.25080\/TCWV9851"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp163"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/isbn.978-3-318-01493-8"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136417"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1319610"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/358764a0"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1149"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl479"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300292"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01369"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1201\/b15410"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1109\/RBME.2010.2083647"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbn058"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-S1-S13"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-205"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1266"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bas015"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035187"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1008"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1114"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12984","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12984","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.12984","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12984","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T17:07:52Z","timestamp":1751735272000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12984"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,6]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/imm.12984"],"URL":"https:\/\/doi.org\/10.1111\/imm.12984","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,6]]},"assertion":[{"value":"2018-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}