{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:54:45Z","timestamp":1780340085456,"version":"3.54.1"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"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":["2014\/03620-2, 2018\/23693-5 and 2018\/19591-2"],"award-info":[{"award-number":["2014\/03620-2, 2018\/23693-5 and 2018\/19591-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["fellowship"],"award-info":[{"award-number":["fellowship"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ncRNA"],"abstract":"<jats:p>Schistosoma japonicum is a flatworm that causes schistosomiasis, a neglected tropical disease. S. japonicum RNA-Seq analyses has been previously reported in the literature on females and males obtained during sexual maturation from 14 to 28 days post-infection in mouse, resulting in the identification of protein-coding genes and pathways, whose expression levels were related to sexual development. However, this work did not include an analysis of long non-coding RNAs (lncRNAs). Here, we applied a pipeline to identify and annotate lncRNAs in 66 S. japonicum RNA-Seq publicly available libraries, from different life-cycle stages. We also performed co-expression analyses to find stage-specific lncRNAs possibly related to sexual maturation. We identified 12,291 S. japonicum expressed lncRNAs. Sequence similarity search and synteny conservation indicated that some 14% of S. japonicum intergenic lncRNAs have synteny conservation with S. mansoni intergenic lncRNAs. Co-expression analyses showed that lncRNAs and protein-coding genes in S. japonicum males and females have a dynamic co-expression throughout sexual maturation, showing differential expression between the sexes; the protein-coding genes were related to the nervous system development, lipid and drug metabolism, and overall parasite survival. Co-expression pattern suggests that lncRNAs possibly regulate these processes or are regulated by the same activation program as that of protein-coding genes.<\/jats:p>","DOI":"10.3390\/ncrna6020015","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T11:57:14Z","timestamp":1585828634000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Dynamic Expression of Long Non-Coding RNAs Throughout Parasite Sexual and Neural Maturation in Schistosoma Japonicum"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-7072","authenticated-orcid":false,"given":"Lucas","family":"Maciel","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Express\u00e3o G\u00eanica em Eucariotos, Instituto Butantan, S\u00e3o Paulo SP 05503-900, Brazil"},{"name":"Programa Interunidades em Bioinform\u00e1tica, Instituto de Matem\u00e1tica e Estat\u00edstica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo SP 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Morales-Vicente","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Express\u00e3o G\u00eanica em Eucariotos, Instituto Butantan, S\u00e3o Paulo SP 05503-900, Brazil"},{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo SP 05508-900, 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 Express\u00e3o G\u00eanica em Eucariotos, Instituto Butantan, S\u00e3o Paulo SP 05503-900, Brazil"},{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo SP 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2015). Investing to Overcome the Global Impact of Neglected Tropical Diseases: Third WHO Report on Neglected Tropical Diseases 2015, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/0014-4894(76)90022-9","article-title":"Intermediate host specificity in Schistosoma mansoni","volume":"39","author":"Basch","year":"1976","journal-title":"Exp. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31150","DOI":"10.1038\/srep31150","article-title":"Schistosome sex matters: A deep view into gonad-specific and pairing-dependent transcriptomes reveals a complex gender interplay","volume":"6","author":"Lu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-018-0013-8","article-title":"Schistosomiasis","volume":"4","author":"McManus","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4269\/ajtmh.1994.50.281","article-title":"Kinetics of Egg Production and Egg Excretion by Schistosoma mansoni and S. japonicum in Mice Infected with a Single Pair of Worms","volume":"50","author":"Cheever","year":"1994","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/sj.icb.7100014","article-title":"Immunopathology of schistosomiasis","volume":"85","author":"Wilson","year":"2007","journal-title":"Immunol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14693","DOI":"10.1038\/ncomms14693","article-title":"Dynamic transcriptomes identify biogenic amines and insect-like hormonal regulation for mediating reproduction in Schistosoma japonicum","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.tig.2018.06.002","article-title":"Strategies to Annotate and Characterize Long Noncoding RNAs: Advantages and Pitfalls","volume":"34","author":"Cao","year":"2018","journal-title":"Trends Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.exppara.2018.07.001","article-title":"Identification of long noncoding RNAs in Schistosoma mansoni and Schistosoma japonicum","volume":"191","author":"Liao","year":"2018","journal-title":"Exp. Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/mrd.22581","article-title":"Long non-coding RNA regulation of reproduction and development","volume":"82","author":"Taylor","year":"2015","journal-title":"Mol. Reprod. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"823","DOI":"10.3389\/fgene.2019.00823","article-title":"Weighted Gene Co-Expression Analyses Point to Long Non-Coding RNA Hub Genes at Different Schistosoma mansoni Life-Cycle Stages","volume":"10","author":"Maciel","year":"2019","journal-title":"Front. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Luo, F., Yin, M., Mo, X., Sun, C., Wu, Q., Zhu, B., Xiang, M., Wang, J., Wang, Y., and Li, J. (2019). An improved genome assembly of the fluke Schistosoma japonicum. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007612"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10508","DOI":"10.1038\/s41598-017-10853-6","article-title":"The Schistosoma mansoni genome encodes thousands of long non-coding RNAs predicted to be functional at different parasite life-cycle stages","volume":"7","author":"Vasconcelos","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nature12943","article-title":"The evolution of lncRNA repertoires and expression patterns in tetrapods","volume":"505","author":"Necsulea","year":"2014","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Herrera-Ubeda, C., Marin-Barba, M., Navas-Perez, E., Gravemeyer, J., Albuixech-Crespo, B., Wheeler, G.N., and Garcia-Fernandez, J. (2019). Microsyntenic Clusters Reveal Conservation of lncRNAs in Chordates Despite Absence of Sequence Conservation. Biology, 8.","DOI":"10.3390\/biology8030061"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1101\/gr.133009.111","article-title":"Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis","volume":"22","author":"Pauli","year":"2012","journal-title":"Genome Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lefever, S., Anckaert, J., Volders, P.-J., Luypaert, M., Vandesompele, J., and Mestdagh, P. (2017). decodeRNA- predicting non-coding RNA functions using guilt-by-association. Database, 2017.","DOI":"10.1093\/database\/bax042"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2007). Eigengene networks for studying the relationships between co-expression modules. BMC Syst. Biol., 1.","DOI":"10.1186\/1752-0509-1-54"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"796","DOI":"10.3389\/fgene.2019.00796","article-title":"Males, the Wrongly Neglected Partners of the Biologically Unprecedented Male-Female Interaction of Schistosomes","volume":"10","author":"Lu","year":"2019","journal-title":"Front. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/cmi.12444","article-title":"The metabolic control of schistosome egg production","volume":"17","author":"Pearce","year":"2015","journal-title":"Cell. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1590\/S0074-02762009000400013","article-title":"High fat diet has a prominent effect upon the course of chronic schistosomiasis mansoni in mice","volume":"104","author":"Alencar","year":"2009","journal-title":"Mem. Do Inst. Oswaldo Cruz"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Collins, J.J., King, R.S., Cogswell, A., Williams, D.L., and Newmark, P.A. (2011). An atlas for Schistosoma mansoni organs and life-cycle stages using cell type-specific markers and confocal microscopy. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001009"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e35449","DOI":"10.7554\/eLife.35449","article-title":"Stem cell heterogeneity drives the parasitic life cycle of Schistosoma mansoni","volume":"7","author":"Wang","year":"2018","journal-title":"ELife"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Diaz Soria, C.L., Lee, J., Chong, T., Coghlan, A., Tracey, A., Young, M.D., Andrews, T., Hall, C., Ng, B.L., and Rawlinson, K. (2019). Single-cell atlas of the first intra-mammalian developmental stage of the human parasite Schistosoma mansoni. bioRxiv.","DOI":"10.1101\/754713"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wangwiwatsin, A., Protasio, A.V., Wilson, S., Owusu, C., Holroyd, N.E., Sanders, M.J., Keane, J., Doenhoff, M.J., Rinaldi, G., and Berriman, M. (2019). Transcriptome of the parasitic flatworm Schistosoma mansoni during intra-mammalian development. bioRxiv.","DOI":"10.1101\/757633"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1080\/15476286.2019.1572438","article-title":"Transcriptomic analyses reveal groups of co-expressed, syntenic lncRNAs in four species of the genus Caenorhabditis","volume":"16","author":"Pegueroles","year":"2019","journal-title":"RNA Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Anguera, M.C., Ma, W., Clift, D., Namekawa, S., Kelleher, R.J., and Lee, J.T. (2011). Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002248"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.tplants.2017.12.009","article-title":"lncRNAs in Plant and Animal Sexual Reproduction","volume":"23","author":"Golicz","year":"2018","journal-title":"Trends Plant Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e43660","DOI":"10.7554\/eLife.43660","article-title":"The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system","volume":"8","author":"Lawson","year":"2019","journal-title":"ELife"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s41586-019-1341-x","article-title":"Developmental dynamics of lncRNAs across mammalian organs and species","volume":"571","author":"Sarropoulos","year":"2019","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrd.2016.117","article-title":"Non-coding RNAs as drug targets","volume":"16","author":"Matsui","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1080\/17460441.2018.1501024","article-title":"Developments in lncRNA drug discovery: Where are we heading?","volume":"13","author":"Blokhin","year":"2018","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3389\/fgene.2019.00205","article-title":"RNA Biology Provides New Therapeutic Targets for Human Disease","volume":"10","author":"Harries","year":"2019","journal-title":"Front. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"i884","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_37","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_38","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_39","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/nbt.4020","article-title":"Accurate assembly of transcripts through phase-preserving graph decomposition","volume":"35","author":"Shao","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_41","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":"2016","journal-title":"Nat. Methods"},{"key":"ref_42","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_43","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_44","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1093\/molbev\/msx148","article-title":"Fast Genome-Wide Functional Annotation through Orthology Assignment by eggNOG-Mapper","volume":"34","author":"Forslund","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"D766","DOI":"10.1093\/nar\/gky955","article-title":"GENCODE reference annotation for the human and mouse genomes","volume":"47","author":"Frankish","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Farrer, R.A. (2017). Synima: A Synteny imaging tool for annotated genome assemblies. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1939-7"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1101\/gr.1224503","article-title":"OrthoMCL: Identification of ortholog groups for eukaryotic genomes","volume":"13","author":"Li","year":"2003","journal-title":"Genome Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3643","DOI":"10.1093\/bioinformatics\/bth397","article-title":"DAGchainer: A tool for mining segmental genome duplications and synteny","volume":"20","author":"Haas","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: A flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_51","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_52","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_53","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1093\/bioinformatics\/bti551","article-title":"BiNGO: A Cytoscape plugin to assess overrepresentation of Gene Ontology categories in Biological Networks","volume":"21","author":"Maere","year":"2005","journal-title":"Bioinformatics"}],"container-title":["Non-Coding RNA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2311-553X\/6\/2\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:14:11Z","timestamp":1760174051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2311-553X\/6\/2\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":53,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ncrna6020015"],"URL":"https:\/\/doi.org\/10.3390\/ncrna6020015","relation":{},"ISSN":["2311-553X"],"issn-type":[{"value":"2311-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,1]]}}}