{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T08:42:32Z","timestamp":1772268152044,"version":"3.50.1"},"reference-count":79,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The ZIKA virus (ZIKV) belongs to the\n                      <jats:italic>Flaviviridae<\/jats:italic>\n                      family, was first isolated in the 1940s, and remained underreported until its global threat in 2016, where drastic consequences were reported as Guillan-Barre syndrome and microcephaly in newborns. Understanding molecular interactions of ZIKV proteins during the host infection is important to develop treatments and prophylactic measures; however, large-scale experimental approaches normally used to detect protein-protein interaction (PPI) are onerous and labor-intensive. On the other hand, computational methods may overcome these challenges and guide traditional approaches on one or few protein molecules. The prediction of PPIs can be used to study host-parasite interactions at the protein level and reveal key pathways that allow viral infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Applying Random Forest and Support Vector Machine (SVM) algorithms, we performed predictions of PPI between two ZIKV strains and human proteomes. The consensus number of predictions of both algorithms was 17,223 pairs of proteins. Functional enrichment analyses were executed with the predicted networks to access the biological meanings of the protein interactions. Some pathways related to viral infection and neurological development were found for both ZIKV strains in the enrichment analysis, but the JAK-STAT pathway was observed only for strain PE243 when compared with the FSS13025 strain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The consensus network of PPI predictions made by Random Forest and SVM algorithms allowed an enrichment analysis that corroborates many aspects of ZIKV infection. The enrichment results are mainly related to viral infection, neuronal development, and immune response, and presented differences among the two compared ZIKV strains. Strain PE243 presented more predicted interactions between proteins from the JAK-STAT signaling pathway, which could lead to a more inflammatory immune response when compared with the FSS13025 strain. These results show that the methodology employed in this study can potentially reveal new interactions between the ZIKV and human cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.11770","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T04:05:51Z","timestamp":1629777951000},"page":"e11770","source":"Crossref","is-referenced-by-count":4,"title":["<i>In silico<\/i>\n                    predictions of protein interactions between Zika virus and human host"],"prefix":"10.7717","volume":"9","author":[{"given":"Jo\u00e3o Luiz de Lemos Padilha","family":"Pitta","sequence":"first","affiliation":[{"name":"Microbiology Department, Aggeu Magalh\u00e3es Institute-FIOCRUZ\/PE, Recife, PE, Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crhisllane Rafaele dos Santos","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Genetics Department, Federal University of Pernambuco, Recife, PE, Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1419-5713","authenticated-orcid":true,"given":"Gabriel da Luz","family":"Wallau","sequence":"additional","affiliation":[{"name":"Entomology Department, Aggeu Magalh\u00e3es Institute-FIOCRUZ\/PE, Recife, PE, Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0446-848X","authenticated-orcid":true,"given":"T\u00falio de Lima","family":"Campos","sequence":"additional","affiliation":[{"name":"Bioinformatics Platform, Aggeu Magalh\u00e3es Institute-FIOCRUZ\/PE, Recife, PE, Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4775-1779","authenticated-orcid":true,"given":"Antonio Mauro","family":"Rezende","sequence":"additional","affiliation":[{"name":"Microbiology Department, Aggeu Magalh\u00e3es Institute-FIOCRUZ\/PE, Recife, PE, Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"issue":"10","key":"10.7717\/peerj.11770\/ref-1","doi-asserted-by":"publisher","first-page":"5018","DOI":"10.1073\/pnas.94.10.5018","article-title":"Cross-validated maximum likelihood enhances crystallographic simulated annealing refinement","volume":"94","author":"Adams","year":"1997","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.7717\/peerj.11770\/ref-2","doi-asserted-by":"publisher","first-page":"4159","DOI":"10.1093\/bioinformatics\/bty504","article-title":"Prediction of human-Bacillus anthracis protein\u2013protein interactions using multi-layer neural network","volume":"34","author":"Ahmed","year":"2018","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"5","key":"10.7717\/peerj.11770\/ref-3","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1111\/aji.12578","article-title":"HSV-2 enhances ZIKV infection of the placenta and induces apoptosis in first-trimester trophoblast cells","volume":"76","author":"Aldo","year":"2016","journal-title":"American Journal of Reproductive Immunology"},{"issue":"6304","key":"10.7717\/peerj.11770\/ref-4","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.antiviral.2017.06.001","article-title":"Zika in the Americas, year 2: what have we learned? 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