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This study aimed to enhance serological diagnosis and discover new drugs by identifying immunogenic protein regions of DENV. Utilizing a comprehensive approach, the study focused on peptides capable of distinguishing DENV from other flavivirus infections through serological analyses. Over 200 patients with confirmed arbovirus infection were profiled using high\u2010density pan flavivirus peptide arrays comprising 6253 peptides and the computational method matrix of local coupling energy (MLCE). Twenty\u2010four peptides from nonstructural and structural viral proteins were identified as specifically recognized by individuals with DENV infection. Six peptides were confirmed to distinguish DENV from Zika virus (ZIKV), West Nile virus (WNV), Yellow Fever virus (YFV), Usutu virus (USUV), and Chikungunya virus (CHIKV) infections, as well as healthy controls. Moreover, the combination of two immunogenic peptides emerged as a potential serum biomarker for DENV infection. These peptides, mapping to highly accessible regions on protein structures, show promise for diagnostic and prophylactic strategies against flavivirus infections. The described methodology holds broader applicability in the serodiagnosis of infectious diseases.<\/jats:p>","DOI":"10.1002\/jmv.29923","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T07:43:28Z","timestamp":1726645408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["High\u2010throughput peptide array analysis and computational techniques for serological profiling of flavivirus infections: Implications for diagnostics and vaccine development"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-4165","authenticated-orcid":false,"given":"Mauro","family":"Bombaci","sequence":"first","affiliation":[{"name":"Istituto Nazionale Genetica Molecolare Padiglione Romeo ed Enrica Invernizzi  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6282-4273","authenticated-orcid":false,"given":"Enrico Mario Alessandro","family":"Fassi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 degli Studi di Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8846-4656","authenticated-orcid":false,"given":"Andrea","family":"Gobbini","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Genetica Molecolare Padiglione Romeo ed Enrica Invernizzi  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9414-0287","authenticated-orcid":false,"given":"Davide","family":"Mileto","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology, Virology and Bioemergencies ASST Fatebenefratelli Sacco \u2010 L. 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