{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:22Z","timestamp":1787030722440,"version":"build-2736575974"},"reference-count":73,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/23693-5"],"award-info":[{"award-number":["2018\/23693-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/06005-0"],"award-info":[{"award-number":["2021\/06005-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2024\/16545-0"],"award-info":[{"award-number":["2024\/16545-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2025\/10237-5"],"award-info":[{"award-number":["2025\/10237-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2024\/16644-9"],"award-info":[{"award-number":["2024\/16644-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2018\/23693-5"],"award-info":[{"award-number":["2018\/23693-5"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2021\/06005-0"],"award-info":[{"award-number":["2021\/06005-0"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024\/16545-0"],"award-info":[{"award-number":["2024\/16545-0"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2025\/10237-5"],"award-info":[{"award-number":["2025\/10237-5"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024\/16644-9"],"award-info":[{"award-number":["2024\/16644-9"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005942","name":"Funda\u00e7\u00e3o Butantan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005942","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["CNPq 313781\/2025-7"],"award-info":[{"award-number":["CNPq 313781\/2025-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"award":["CNPq 313781\/2025-7"],"award-info":[{"award-number":["CNPq 313781\/2025-7"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The human placenta plays a critical role as an immune and mechanical barrier. Notwithstanding, viral pathogens can still cross this barrier. Previously, differential gene expression has been described for protein-coding genes in human-induced-pluripotent-stem-cell-derived (hiPSC-derived) trophoblasts (TBs) from dizygotic twins discordant for congenital Zika syndrome (CZS), in which only one of the twin subjects presented the microcephaly phenotype. However, the involvement of long non-coding RNAs (lncRNAs) in TB development and in the TB response to ZIKV infection remained unexplored. To address this gap, we constructed a trophoblast-specific, lncRNA-enriched transcriptome resource and used it to define co-expression networks linking lncRNAs to trophoblast differentiation and to the antiviral response to ZIKV infection. Here, public RNA-Seq data from hiPSCs and hiPSC-derived TBs from dizygotic twins discordant for CZS were re-mapped to the human reference genome (GRCh38) using an ad hoc compiled hiPSC-TB-specific transcriptome enriched for lncRNAs, followed by differential expression analysis, co-expression network analysis and gene ontology (GO) enrichment. Expression validation by RT-qPCR of a set of novel and known lncRNAs associated with trophoblast differentiation and ZIKV infection was obtained. When comparing hiPSCs and TBs, 218 known and 26 novel lncRNAs were differentially expressed (DE) (FDR &lt; 0.001). Correlated modules were enriched with GO terms related to \u201cepithelial cell differentiation\u201d and \u201ctissue morphogenesis\u201d. Upon comparing TBs derived from the dizygotic twins, before and after ZIKV infection, 96 known and 6 novel lncRNAs were DE (FDR &lt; 0.05). Correlated modules were enriched with interferon-related GO terms, including \u201cregulation of defense response to virus\u201d and \u201cresponse to interferon\u201d. ZIKV-infected TBs from microcephaly-affected twins showed a 2.5-fold lower number of DE protein-coding genes and a 2-fold lower number of DE lncRNAs, compared with ZIKV-infected TBs from non-affected twins. These results indicate lncRNAs associated with TB development and response to ZIKV infection, highlighting candidates to be prioritized in future functional studies, such as CARINH, PSMB8-AS1, HCP5, BISPR and imprinted H19 and MEG3 lncRNAs.<\/jats:p>","DOI":"10.3390\/ijms27167281","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Co-Expression Network Analyses Reveal Long Non-Coding RNA Programs Associated with Trophoblast Development and Response to Zika Virus Infection in Twins Discordant for Congenital Zika Syndrome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2923-6335","authenticated-orcid":false,"given":"Thalles","family":"Souza-Lopes","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Programa Interunidades de P\u00f3s-Gradua\u00e7\u00e3o em Bioinform\u00e1tica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2481-2387","authenticated-orcid":false,"given":"Agatha","family":"Fischer-Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4059-3820","authenticated-orcid":false,"given":"Caio F.","family":"Freire","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Programa Interunidades de P\u00f3s-Gradua\u00e7\u00e3o em Bioinform\u00e1tica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5264-3524","authenticated-orcid":false,"given":"Pedro J.","family":"Poli","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2326-9494","authenticated-orcid":false,"given":"Raiane O.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2162-9505","authenticated-orcid":false,"given":"Maria F. C.","family":"Amarante","sequence":"additional","affiliation":[{"name":"Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayana","family":"Zatz","sequence":"additional","affiliation":[{"name":"Instituto de Bioci\u00eancias, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7036-7305","authenticated-orcid":false,"given":"Ana C.","family":"Tahira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4999-5099","authenticated-orcid":false,"given":"Murilo S.","family":"Amaral","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-2401","authenticated-orcid":false,"given":"Sergio","family":"Verjovski-Almeida","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev-virology-031413-085524","article-title":"The Placenta as a Barrier to Viral Infections","volume":"1","author":"Sadovsky","year":"2014","journal-title":"Annu Rev. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S138","DOI":"10.1016\/j.ajog.2015.07.046","article-title":"Placental transcriptome in development and pathology: Expression, function, and methods of analysis","volume":"213","author":"Cox","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s10142-017-0555-y","article-title":"Transcriptome profile of the human placenta","volume":"17","author":"Majewska","year":"2017","journal-title":"Funct. Integr. Genom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41586-026-10316-x","article-title":"Single-cell spatiotemporal dissection of the human maternal-fetal interface","volume":"653","author":"Wang","year":"2026","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Deyssenroth, M.A., Peng, S., Hao, K., Lambertini, L., Marsit, C.J., and Chen, J. (2017). Whole-transcriptome analysis delineates the human placenta gene network and its associations with fetal growth. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3878-0"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sotcheff, S.L., Chen, J.Y., Elrod, N., Cao, J., Jaworski, E., Kuyumcu-Martinez, M.N., Shi, P.Y., and Routh, A.L. (2022). Zika Virus Infection Alters Gene Expression and Poly-Adenylation Patterns in Placental Cells. Pathogens, 11.","DOI":"10.3390\/pathogens11080936"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1001\/jamaneurol.2016.3720","article-title":"Congenital Zika Virus Infection: Beyond Neonatal Microcephaly","volume":"73","author":"Melo","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18002","DOI":"10.1038\/s41598-024-65392-8","article-title":"Zika virus vertical transmission induces neuroinflammation and synapse impairment in brain cells derived from children born with Congenital Zika Syndrome","volume":"14","author":"Benazzato","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41467-017-02790-9","article-title":"Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells","volume":"9","author":"Goulart","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Amaral, M.S., Goulart, E., Caires-J\u00fanior, L.C., Morales-Vicente, D.A., Soares-Schanoski, A., Gomes, R.P., Olberg, G.G.O., Astray, R.M., Kalil, J.E., and Zatz, M. (2020). Differential gene expression elicited by ZIKV infection in trophoblasts from congenital Zika syndrome discordant twins. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008424"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-1-4939-7471-9_6","article-title":"The Emerging Role of Long Noncoding RNAs in Human Disease","volume":"1706","author":"DiStefano","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mattick, J.S. (2018). The State of Long Non-Coding RNA Biology. Noncoding RNA, 4.","DOI":"10.3390\/ncrna4030017"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"McAninch, D., Roberts, C.T., and Bianco-Miotto, T. (2017). Mechanistic Insight into Long Noncoding RNAs and the Placenta. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071371"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ren, J., Jin, H., and Zhu, Y. (2023). The Role of Placental Non-Coding RNAs in Adverse Pregnancy Outcomes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24055030"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zarkovic, M., Hufsky, F., Markert, U.R., and Marz, M. (2022). The Role of Non-Coding RNAs in the Human Placenta. Cells, 11.","DOI":"10.3390\/cells11091588"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41580-022-00566-8","article-title":"Long non-coding RNAs: Definitions, functions, challenges and recommendations","volume":"24","author":"Mattick","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, T., Li, J., Yang, L., Wu, M., and Ma, Q. (2021). The Role of Long Non-coding RNAs in Human Imprinting Disorders: Prospective Therapeutic Targets. Front Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.730014"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0092-8674(84)90313-1","article-title":"Completion of mouse embryogenesis requires both the maternal and paternal genomes","volume":"37","author":"McGrath","year":"1984","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/308548a0","article-title":"Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis","volume":"308","author":"Surani","year":"1984","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/311374a0","article-title":"Role of paternal and maternal genomes in mouse development","volume":"311","author":"Barton","year":"1984","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/bies.10277","article-title":"Imprinting evolution and the price of silence","volume":"25","author":"Murphy","year":"2003","journal-title":"Bioessays"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1080\/15592294.2022.2091815","article-title":"Genomic map of candidate human imprint control regions: The imprintome","volume":"17","author":"Jima","year":"2022","journal-title":"Epigenetics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bbagrm.2015.05.006","article-title":"Long noncoding RNAs: Lessons from genomic imprinting","volume":"1859","author":"Kanduri","year":"2016","journal-title":"Biochim Biophys. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Barriocanal, M., Carnero, E., Segura, V., and Fortes, P. (2014). Long Non-Coding RNA BST2\/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin. Front Immunol., 5.","DOI":"10.3389\/fimmu.2014.00655"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e202403021","DOI":"10.26508\/lsa.202403021","article-title":"LncRNA CARINH regulates expression and function of innate immune transcription factor IRF1 in macrophages","volume":"8","author":"Cyr","year":"2025","journal-title":"Life Sci. Alliance"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gourvest, M., and van Solingen, C. (2025). CARINH, an Interferon-Induced LncRNA in Cancer and Inflammation. Noncoding RNA, 11.","DOI":"10.3390\/ncrna11060079"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Meng, X.Y., Luo, Y., Anwar, M.N., Sun, Y., Gao, Y., Zhang, H., Munir, M., and Qiu, H.J. (2017). Long Non-Coding RNAs: Emerging and Versatile Regulators in Host-Virus Interactions. Front Immunol., 8.","DOI":"10.3389\/fimmu.2017.01663"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1080\/15476286.2019.1572448","article-title":"Long non-coding RNA PSMB8-AS1 regulates influenza virus replication","volume":"16","author":"More","year":"2019","journal-title":"RNA Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.meegid.2016.03.037","article-title":"Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load","volume":"41","author":"Erikstrup","year":"2016","journal-title":"Infect. Genet Evol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"ISCB\u2013Comm J\u2013304","DOI":"10.12688\/f1000research.23297.1","article-title":"GFF Utilities: GffRead and GffCompare","volume":"9","author":"Pertea","year":"2020","journal-title":"F1000Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1093\/nar\/gkt006","article-title":"CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression model","volume":"41","author":"Wang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"W12","DOI":"10.1093\/nar\/gkx428","article-title":"CPC2: A fast and accurate coding potential calculator based on sequence intrinsic features","volume":"45","author":"Kang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_33","first-page":"e57","article-title":"FEELnc: A tool for long non-coding RNA annotation and its application to the dog transcriptome","volume":"45","author":"Wucher","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"D794","DOI":"10.1093\/nar\/gkx1081","article-title":"The Encyclopedia of DNA elements (ENCODE): Data portal update","volume":"46","author":"Davis","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"Consortium","year":"2020","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"D243","DOI":"10.1093\/nar\/gkae1038","article-title":"NCBI RefSeq: Reference sequence standards through 25 years of curation and annotation","volume":"53","author":"Goldfarb","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s13059-023-03088-4","article-title":"CHESS 3: An improved, comprehensive catalog of human genes and transcripts based on large-scale expression data, phylogenetic analysis, and protein structure","volume":"24","author":"Varabyou","year":"2023","journal-title":"Genome Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nature21374","article-title":"An atlas of human long non-coding RNAs with accurate 5\u2032 ends","volume":"543","author":"Hon","year":"2017","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D1331","DOI":"10.1093\/nar\/gkaf1250","article-title":"The UCSC Genome Browser database: 2026 update","volume":"54","author":"Casper","year":"2026","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Langfelder, P., Luo, R., Oldham, M.C., and Horvath, S. (2011). Is my network module preserved and reproducible?. PLoS Comput. Biol., 7.","DOI":"10.1371\/journal.pcbi.1001057"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_42","first-page":"163","article-title":"Trophoblast invasion and placentation: Molecular mechanisms and regulation","volume":"88","author":"Berndt","year":"2005","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/s41467-022-28663-4","article-title":"A microphysiological model of human trophoblast invasion during implantation","volume":"13","author":"Park","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sheridan, M.A., Zhou, J., Franz, A.W.E., and Schust, D.J. (2022). Modeling the Human Placenta to Investigate Viral Infections During Pregnancy. Front. Virol., 2.","DOI":"10.3389\/fviro.2022.831754"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2016.03.008","article-title":"Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection","volume":"19","author":"Bayer","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E1587","DOI":"10.1073\/pnas.1616097114","article-title":"Vulnerability of primitive human placental trophoblast to Zika virus","volume":"114","author":"Sheridan","year":"2017","journal-title":"Proc. Natl. Acad. Sci.USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12985-025-02729-3","article-title":"The first trimester human placenta responds to Zika virus infection inducing an interferon (IFN) and antiviral interferon stimulated gene (ISG) response","volume":"22","author":"McCullough","year":"2025","journal-title":"Virol. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1600-0897.2008.00601.x","article-title":"Genetic predisposition to idiopathic recurrent spontaneous abortion: Contribution of genetic variations in IGF-2 and H19 imprinted genes","volume":"60","author":"Ostojic","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9006","DOI":"10.1002\/jcb.28172","article-title":"Silencing H19 regulated proliferation, invasion, and autophagy in the placenta by targeting miR-18a-5p","volume":"120","author":"Zhang","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/mrd.23147","article-title":"LncRNA MEG3 inhibits trophoblast invasion and trophoblast-mediated VSMC loss in uterine spiral artery remodeling","volume":"86","author":"Tao","year":"2019","journal-title":"Mol. Reprod. Dev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1002\/jcb.25004","article-title":"Down-regulated long non-coding RNA MEG3 and its effect on promoting apoptosis and suppressing migration of trophoblast cells","volume":"116","author":"Zhang","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nature18296","article-title":"The Brazilian Zika virus strain causes birth defects in experimental models","volume":"534","author":"Cugola","year":"2016","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1080\/22221751.2020.1753583","article-title":"Zika structural genes determine the virulence of African and Asian lineages","volume":"9","author":"Nunes","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ebiom.2016.09.020","article-title":"Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells","volume":"12","author":"Simonin","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_55","unstructured":"(2023, October 08). SRA_Toolkit_Development_Team. NCBI SRA Tools: The NCBI SRA (Sequence Read Archive). Available online: https:\/\/github.com\/ncbi\/sra-tools."},{"key":"ref_56","unstructured":"Andrews, S. (2023, October 08). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"D966","DOI":"10.1093\/nar\/gkae1078","article-title":"GENCODE 2025: Reference gene annotation for human and mouse","volume":"53","author":"Mudge","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1093\/bioinformatics\/bts356","article-title":"RSeQC: Quality control of RNA-seq experiments","volume":"28","author":"Wang","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nmeth.4078","article-title":"TACO produces robust multisample transcriptome assemblies from RNA-seq","volume":"14","author":"Niknafs","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"EdgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_67","first-page":"1","article-title":"The igraph software package for complex network research","volume":"1695","author":"Csardi","year":"2006","journal-title":"Inter J. Complex Syst."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.tibtech.2018.12.002","article-title":"The Ultimate qPCR Experiment: Producing Publication Quality, Reproducible Data the First Time","volume":"37","author":"Taylor","year":"2019","journal-title":"Trends Biotechnol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"16816","DOI":"10.1038\/s41598-021-96055-7","article-title":"Assessment of reference genes at six different developmental stages of Schistosoma mansoni for quantitative RT-PCR","volume":"11","author":"Silveira","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_71","unstructured":"R Core Team (2023, October 08). A Language and Environment for Statistical Computing. Available online: http:\/\/www.R-project.org\/."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1214\/aos\/1013699998","article-title":"The Control of the False Discovery Rate in Multiple Testing under Dependency","volume":"29","author":"Benjamini","year":"2001","journal-title":"Ann. Stat."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:27:35Z","timestamp":1787027255000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,15]]},"references-count":73,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167281"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167281","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,15]]}}}