{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:28Z","timestamp":1787022208071,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010399","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000}}],"reference-count":101,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI151171"],"award-info":[{"award-number":["R01 AI151171"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UW SciMed GRS Fellowship"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI007414"],"award-info":[{"award-number":["T32 AI007414"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F32 AI152347"],"award-info":[{"award-number":["F32 AI152347"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Lymphatic filariasis (LF) is a chronic debilitating neglected tropical disease (NTD) caused by mosquito-transmitted nematodes that afflicts over 60 million people. Control of LF relies on routine mass drug administration with antiparasitics that clear circulating larval parasites but are ineffective against adults. The development of effective adulticides is hampered by a poor understanding of the processes and tissues driving parasite survival in the host. The adult filariae head region contains essential tissues that control parasite feeding, sensory, secretory, and reproductive behaviors, which express promising molecular substrates for the development of antifilarial drugs, vaccines, and diagnostics. We have adapted spatial transcriptomic approaches to map gene expression patterns across these prioritized but historically intractable head tissues. Spatial and tissue-resolved data reveal distinct biases in the origins of known drug targets and secreted antigens. These data were used to identify potential new drug and vaccine targets, including putative hidden antigens expressed in the alimentary canal, and to spatially associate receptor subunits belonging to druggable families. Spatial transcriptomic approaches provide a powerful resource to aid gene function inference and seed antiparasitic discovery pipelines across helminths of relevance to human and animal health.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010399","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T14:11:13Z","timestamp":1649340673000},"page":"e1010399","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Spatial transcriptomics reveals antiparasitic targets associated with essential behaviors in the human parasite Brugia malayi"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-006X","authenticated-orcid":true,"given":"Paul M.","family":"Airs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Vaccaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra J.","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5843-2584","authenticated-orcid":true,"given":"Nathalie","family":"Dinguirard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3455-383X","authenticated-orcid":true,"given":"Zachary W.","family":"Heimark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5909-4190","authenticated-orcid":true,"given":"Nicolas J.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-3937","authenticated-orcid":true,"given":"Kurt R.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-2136","authenticated-orcid":true,"given":"Nathan E.","family":"Schroeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7250-3756","authenticated-orcid":true,"given":"Jan","family":"Huisken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9233-1760","authenticated-orcid":true,"given":"Mostafa","family":"Zamanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,7]]},"reference":[{"key":"ppat.1010399.ref001","volume-title":"Guideline: Alternative Mass Drug Administration Regimens to Eliminate Lymphatic Filariasis","author":"WHO","year":"2018"},{"key":"ppat.1010399.ref002","first-page":"457","article-title":"Global programme to eliminate lymphatic filariasis: progress report, 2018\u2014Programme mondial pour l\u2019\u00e9limination de la filariose lymphatique: rapport de situation, 2018","volume":"94","author":"Organisation mondiale de la Sant\u00e9.,WHO","year":"2019","journal-title":"Weekly Epidemiological Record = Relev\u00e9 \u00e9pid\u00e9miologique hebdomadaire"},{"key":"ppat.1010399.ref003","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"SL James","year":"2018","journal-title":"Lancet"},{"key":"ppat.1010399.ref004","volume-title":"Gerald D. Schmidt & Larry S. Roberts\u2019 Foundations of Parasitology","author":"LS Roberts","year":"2009"},{"key":"ppat.1010399.ref005","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40249-015-0068-7","article-title":"The burden of mental health in lymphatic filariasis","volume":"4","author":"TGN Ton","year":"2015","journal-title":"Infect Dis Poverty"},{"key":"ppat.1010399.ref006","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.1371\/journal.pntd.0000237","article-title":"Stigma and the social burden of neglected tropical diseases","volume":"2","author":"MG Weiss","year":"2008","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref007","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1001\/jama.1988.03720210040026","article-title":"Ivermectin for the treatment of Wuchereria bancrofti filariasis. Efficacy and adverse reactions","volume":"259","author":"V Kumaraswami","year":"1988","journal-title":"JAMA"},{"key":"ppat.1010399.ref008","doi-asserted-by":"crossref","first-page":"e998","DOI":"10.1371\/journal.pntd.0000998","article-title":"Phenotypic evidence of emerging ivermectin resistance in Onchocerca volvulus","volume":"5","author":"MY Osei-Atweneboana","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref009","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1017\/S003118201500061X","article-title":"The emergence of macrocyclic lactone resistance in the canine heartworm, Dirofilaria immitis","volume":"142","author":"AJ Wolstenholme","year":"2015","journal-title":"Parasitology"},{"key":"ppat.1010399.ref010","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.vetpar.2015.04.002","article-title":"Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance","volume":"210","author":"C Bourguinat","year":"2015","journal-title":"Vet Parasitol"},{"key":"ppat.1010399.ref011","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.vetpar.2011.04.012","article-title":"Macrocyclic lactone resistance in Dirofilaria immitis","volume":"181","author":"C Bourguinat","year":"2011","journal-title":"Vet Parasitol"},{"key":"ppat.1010399.ref012","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.pt.2004.07.010","article-title":"Drug resistance in veterinary helminths","volume":"20","author":"AJ Wolstenholme","year":"2004","journal-title":"Trends Parasitol"},{"key":"ppat.1010399.ref013","article-title":"When Secretomes Meet Anthelmintics: Lessons for Therapeutic Interventions","author":"Y Moreno","year":"2021","journal-title":"Trends Parasitol"},{"key":"ppat.1010399.ref014","doi-asserted-by":"crossref","first-page":"e12036","DOI":"10.1002\/jev2.12036","article-title":"Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes","volume":"10","author":"HJ Loghry","year":"2020","journal-title":"J Extracell Vesicles"},{"key":"ppat.1010399.ref015","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.vetpar.2014.02.004","article-title":"Ivermectin-dependent attachment of neutrophils and peripheral blood mononuclear cells to Dirofilaria immitis microfilariae in vitro","volume":"206","author":"AF Vatta","year":"2014","journal-title":"Vet Parasitol"},{"key":"ppat.1010399.ref016","doi-asserted-by":"crossref","first-page":"20120","DOI":"10.1073\/pnas.1011983107","article-title":"Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi","volume":"107","author":"Y Moreno","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010399.ref017","doi-asserted-by":"crossref","first-page":"e0006438","DOI":"10.1371\/journal.pntd.0006438","article-title":"Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin","volume":"12","author":"H Harischandra","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref018","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1090-0233(05)80005-X","article-title":"Modes of action of anthelmintic drugs","volume":"154","author":"RJ Martin","year":"1997","journal-title":"Vet J"},{"key":"ppat.1010399.ref019","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1007\/s00436-014-3829-5","article-title":"Intraperitoneal development of the filarial nematode Brugia malayi in the Mongolian jird (Meriones unguiculatus)","volume":"113","author":"Y Mutafchiev","year":"2014","journal-title":"Parasitol Res"},{"key":"ppat.1010399.ref020","doi-asserted-by":"crossref","first-page":"e1409","DOI":"10.1371\/journal.pntd.0001409","article-title":"A deep sequencing approach to comparatively analyze the transcriptome of lifecycle stages of the filarial worm, Brugia malayi","volume":"5","author":"YJ Choi","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref021","unstructured":"Cotten MA. Analysis of the microfilariae-specific transcriptome of Brugia pahangi during mosquito infection. 2016. Available: https:\/\/baylor-ir.tdl.org\/handle\/2104\/9646."},{"key":"ppat.1010399.ref022","doi-asserted-by":"crossref","first-page":"e0005357","DOI":"10.1371\/journal.pntd.0005357","article-title":"Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq","volume":"11","author":"A Grote","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref023","first-page":"7","article-title":"Multispecies Transcriptomics Data Set of Brugia malayi, Its Wolbachia Endosymbiont wBm, and Aedes aegypti across the B. malayi Life Cycle","author":"M Chung","year":"2018","journal-title":"Microbiol Resour Announc"},{"key":"ppat.1010399.ref024","doi-asserted-by":"crossref","first-page":"e0004929","DOI":"10.1371\/journal.pntd.0004929","article-title":"The Effects of Ivermectin on Brugia malayi Females In Vitro: A Transcriptomic Approach","volume":"10","author":"C Ballesteros","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref025","doi-asserted-by":"crossref","first-page":"e0004311","DOI":"10.1371\/journal.pntd.0004311","article-title":"The Effect of In Vitro Cultivation on the Transcriptome of Adult Brugia malayi","volume":"10","author":"C Ballesteros","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref026","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1186\/1471-2164-10-267","article-title":"Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3","volume":"10","author":"BW Li","year":"2009","journal-title":"BMC Genomics"},{"key":"ppat.1010399.ref027","first-page":"5","article-title":"Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)","author":"MJ Maclean","year":"2019","journal-title":"Parasitology Open"},{"key":"ppat.1010399.ref028","doi-asserted-by":"crossref","first-page":"e0004054","DOI":"10.1371\/journal.pntd.0004054","article-title":"A Proteomic Analysis of the Body Wall, Digestive Tract, and Reproductive Tract of Brugia malayi","volume":"9","author":"CP Morris","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref029","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.cell.2014.09.038","article-title":"Genome-wide RNA Tomography in the zebrafish embryo","volume":"159","author":"JP Junker","year":"2014","journal-title":"Cell"},{"key":"ppat.1010399.ref030","article-title":"Spatial Transcriptomics of C. elegans Males and Hermaphrodites Identifies Sex-Specific Differences in Gene Expression Patterns","author":"A Ebbing","year":"2018","journal-title":"Developmental Cell"},{"key":"ppat.1010399.ref031","doi-asserted-by":"crossref","first-page":"e410","DOI":"10.1371\/journal.pntd.0000410","article-title":"Brugia malayi excreted\/secreted proteins at the host\/parasite interface: stage- and gender-specific proteomic profiling","volume":"3","author":"S Bennuru","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref032","doi-asserted-by":"crossref","first-page":"e326","DOI":"10.1371\/journal.pntd.0000326","article-title":"Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products","volume":"2","author":"Y Moreno","year":"2008","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref033","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1128\/CMR.00002-13","article-title":"A comprehensive, model-based review of vaccine and repeat infection trials for filariasis","volume":"26","author":"CP Morris","year":"2013","journal-title":"Clin Microbiol Rev"},{"key":"ppat.1010399.ref034","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1046\/j.1365-3024.1996.d01-10.x","article-title":"Characterization of a secreted antigen of Onchocerca volvulus with host-protective potential","volume":"18","author":"RE Jenkins","year":"1996","journal-title":"Parasite Immunol"},{"key":"ppat.1010399.ref035","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.4049\/jimmunol.143.10.3359","article-title":"Paramyosin-enhanced clearance of Brugia malayi microfilaremia in mice","volume":"143","author":"J Nanduri","year":"1989","journal-title":"J Immunol"},{"key":"ppat.1010399.ref036","article-title":"Functional investigation of conserved glutamate receptor subunits reveals a new mode of action of macrocyclic lactones in nematodes","author":"N Lamassiaude","year":"2020","journal-title":"bioRxiv"},{"key":"ppat.1010399.ref037","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ijpddr.2014.01.002","article-title":"High level expression of a glutamate-gated chloride channel gene in reproductive tissues of Brugia malayi may explain the sterilizing effect of ivermectin on filarial worms","volume":"4","author":"BW Li","year":"2014","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"ppat.1010399.ref038","doi-asserted-by":"crossref","first-page":"e1009682","DOI":"10.1371\/journal.ppat.1009682","article-title":"Development of emodepside as a possible adulticidal treatment for human onchocerciasis\u2014The fruit of a successful industrial\u2013academic collaboration","volume":"17","author":"J Kr\u00fccken","year":"2021","journal-title":"PLoS Pathog"},{"key":"ppat.1010399.ref039","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0022149X00032922","article-title":"On the Adult Morphology of Wuchereria sp. (malayi?) from a Monkey (Macaca irus) and from Cats in Malaya, and on Wuchereria pahangi n.sp. from a Dog and a Cat","author":"JJC Buckley","year":"1956","journal-title":"Journal of Helminthology"},{"key":"ppat.1010399.ref040","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/0014-4894(81)90041-2","article-title":"Brugia pahangi: feeding and nutrient uptake in vitro and in vivo","volume":"51","author":"RE Howells","year":"1981","journal-title":"Exp Parasitol"},{"key":"ppat.1010399.ref041","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2307\/3275301","article-title":"Morphology of the larval stages of Dirofilaria immitis in the dog","volume":"47","author":"TC Orihel","year":"1961","journal-title":"J Parasitol"},{"key":"ppat.1010399.ref042","doi-asserted-by":"crossref","first-page":"693","DOI":"10.2307\/3275258","article-title":"Developmental stages of Brugia pahangi in the final host","volume":"48","author":"JF Schacher","year":"1962","journal-title":"J Parasitol"},{"key":"ppat.1010399.ref043","doi-asserted-by":"crossref","first-page":"499","DOI":"10.2307\/3279332","article-title":"The Ultrastructure of Adult Brugia malayi (Brug, 1927) (Nematoda: Filarioidea)","volume":"61","author":"AL Vincent","year":"1975","journal-title":"J Parasitol"},{"key":"ppat.1010399.ref044","first-page":"219","article-title":"Ultrastructural studies on the microfilaria of Brugia malayi","volume":"28","author":"Y. Tongu","year":"1974","journal-title":"Acta Med Okayama"},{"key":"ppat.1010399.ref045","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2307\/3277892","article-title":"Ultrastructural morphology of the esophageal region of the infective larva of Brugia pahangi (nematoda: Filarioidea)","volume":"57","author":"WK Collin","year":"1971","journal-title":"J Parasitol"},{"key":"ppat.1010399.ref046","doi-asserted-by":"crossref","first-page":"567","DOI":"10.2307\/3279354","article-title":"A Comparison of the Body Wall Ultrastructure of Brugia pahangi with that of Brugia malayi","volume":"61","author":"AL Vincent","year":"1975","journal-title":"J Parasitol"},{"key":"ppat.1010399.ref047","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12862-019-1444-x","article-title":"Improved phylogenomic sampling of free-living nematodes enhances resolution of higher-level nematode phylogeny","volume":"19","author":"AB Smythe","year":"2019","journal-title":"BMC Evol Biol"},{"key":"ppat.1010399.ref048","author":"International Helminth Genomes Consortium","journal-title":"Comparative genomics of the major parasitic worms"},{"key":"ppat.1010399.ref049","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/BF00931502","article-title":"Ultrastructure study of the excretory system and the genital primordium of the infective stage of Onchocerca volvulus (Nematoda:Filarioidea)","volume":"81","author":"G Strote","year":"1995","journal-title":"Parasitol Res"},{"key":"ppat.1010399.ref050","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1007\/s00436-013-3483-3","article-title":"Ecological, morphological, and molecular studies of Acanthocheilonema odendhali (Nematoda: Filarioidea) in northern fur seals (Callorhinus ursinus) on St. Paul Island, Alaska","volume":"112","author":"TA Kuzmina","year":"2013","journal-title":"Parasitol Res"},{"key":"ppat.1010399.ref051","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0022-5320(83)90050-3","article-title":"Fine structure of the Caenorhabditis elegans secretory\u2014excretory system","author":"FK Nelson","year":"1983","journal-title":"Journal of Ultrastructure Research"},{"issue":"Pt 1","key":"ppat.1010399.ref052","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1017\/S0031182000066294","article-title":"The ultrastructure of the anterior end of male Onchocerca volvulus: papillae, amphids, nerve ring and first indication of an excretory system in the adult filarial worm","volume":"113","author":"G Strote","year":"1996","journal-title":"Parasitology"},{"key":"ppat.1010399.ref053","doi-asserted-by":"crossref","first-page":"992","DOI":"10.2307\/3279832","article-title":"Transovarially-transmitted intracellular microorganisms in adult and larval stages of Brugia malayi","volume":"63","author":"WJ Kozek","year":"1977","journal-title":"J Parasitol"},{"key":"ppat.1010399.ref054","doi-asserted-by":"crossref","first-page":"e1174","DOI":"10.1371\/journal.pntd.0001174","article-title":"Tissue and stage-specific distribution of Wolbachia in Brugia malayi","volume":"5","author":"K Fischer","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1098\/rstb.1986.0056","article-title":"The structure of the nervous system of the nematode Caenorhabditis elegans","volume":"314","author":"JG White","year":"1986","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ppat.1010399.ref056","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/0012-1606(77)90158-0","article-title":"Post-embryonic cell lineages of the nematode, Caenorhabditis elegans","volume":"56","author":"JE Sulston","year":"1977","journal-title":"Dev Biol"},{"key":"ppat.1010399.ref057","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13227-019-0118-5","article-title":"Convergent evolution of saccate body shapes in nematodes through distinct developmental mechanisms","volume":"10","author":"S Thapa","year":"2019","journal-title":"Evodevo"},{"key":"ppat.1010399.ref058","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0166-6851(01)00374-7","article-title":"Expression and immune recognition of Brugia malayi VAL-1, a homologue of vespid venom allergens and Ancylostoma secreted proteins","volume":"118","author":"J Murray","year":"2001","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1010399.ref059","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/978-1-59745-000-3_23","article-title":"Oocytes as an expression system for studying receptor\/channel targets of drugs and pesticides","volume":"322","author":"SD Buckingham","year":"2006","journal-title":"Methods Mol Biol"},{"key":"ppat.1010399.ref060","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1073\/pnas.97.6.2674","article-title":"The genetics of ivermectin resistance in Caenorhabditis elegans","volume":"97","author":"JA Dent","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010399.ref061","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1006\/expr.1993.1064","article-title":"Haemonchus contortus: ivermectin-induced paralysis of the pharynx","volume":"77","author":"TG Geary","year":"1993","journal-title":"Exp Parasitol"},{"issue":"Pt 5","key":"ppat.1010399.ref062","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1017\/S0031182097001601","article-title":"Actions of the anthelmintic ivermectin on the pharyngeal muscle of the parasitic nematode","volume":"115","author":"DJ Brownlee","year":"1997","journal-title":"Ascaris suum. Parasitology"},{"key":"ppat.1010399.ref063","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10158-012-0135-8","article-title":"Bacterial pore-forming proteins as anthelmintics","volume":"12","author":"Y Hu","year":"2012","journal-title":"Invert Neurosci"},{"key":"ppat.1010399.ref064","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0020-7519(97)00003-9","article-title":"Rational design of nematode vaccines: hidden antigens","volume":"27","author":"EA Munn","year":"1997","journal-title":"Int J Parasitol"},{"key":"ppat.1010399.ref065","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1586\/14760584.2014.893195","article-title":"Vaccination against helminth parasite infections","volume":"13","author":"JP Hewitson","year":"2014","journal-title":"Expert Rev Vaccines"},{"key":"ppat.1010399.ref066","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1073\/pnas.0813048106","article-title":"The G protein-coupled receptor FSHR-1 is required for the Caenorhabditis elegans innate immune response","volume":"106","author":"JR Powell","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010399.ref067","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-021-03634-9","article-title":"Exploring tissue architecture using spatial transcriptomics","author":"A Rao","year":"2021","journal-title":"Nature"},{"key":"ppat.1010399.ref068","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molbiopara.2008.02.007","article-title":"The secretome of the filarial parasite, Brugia malayi: Proteomic profile of adult excretory\u2013secretory products","volume":"160","author":"JP Hewitson","year":"2008","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1010399.ref069","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/bs.apar.2016.02.011","article-title":"Immunity to Haemonchus contortus and Vaccine Development","volume":"93","author":"AJ Nisbet","year":"2016","journal-title":"Adv Parasitol"},{"key":"ppat.1010399.ref070","first-page":"7119","article-title":"Combining single-cell RNA-sequencing with a molecular atlas unveils new markers for Caenorhabditis elegans neuron classes","volume":"48","author":"R Lorenzo","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"ppat.1010399.ref071","doi-asserted-by":"crossref","first-page":"e0006509","DOI":"10.1371\/journal.pntd.0006509","article-title":"Development of a toolkit for piggyBac-mediated integrative transfection of the human filarial parasite Brugia malayi","volume":"12","author":"C Liu","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1010399.ref072","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"ppat.1010399.ref073","doi-asserted-by":"crossref","first-page":"e38011","DOI":"10.1371\/journal.pone.0038011","article-title":"TrakEM2 software for neural circuit reconstruction","volume":"7","author":"A Cardona","year":"2012","journal-title":"PLoS One"},{"key":"ppat.1010399.ref074","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1186\/1471-2105-11-274","article-title":"A high-level 3D visualization API for Java and ImageJ","volume":"11","author":"B Schmid","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"ppat.1010399.ref075","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1083\/jcb.30.2.424","article-title":"A new staining method (OTO) for enhancing contrast of lipid\u2014containing membranes and droplets in osmium tetroxide\u2014fixed tissue with osmiophilic thiocarbohydrazide(TCH)","volume":"30","author":"AM Seligman","year":"1966","journal-title":"J Cell Biol"},{"key":"ppat.1010399.ref076","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1017\/S1431927610055170","article-title":"Enhancing Serial Block-Face Scanning Electron Microscopy to Enable High Resolution 3-D Nanohistology of Cells and Tissues","volume":"16","author":"TJ Deerinck","year":"2010","journal-title":"Microsc Microanal"},{"key":"ppat.1010399.ref077","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1242\/dev.082586","article-title":"Multilayer mounting enables long-term imaging of zebrafish development in a light sheet microscope","volume":"139","author":"A Kaufmann","year":"2012","journal-title":"Development"},{"key":"ppat.1010399.ref078","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1364\/OL.32.002608","article-title":"Even fluorescence excitation by multidirectional selective plane illumination microscopy (mSPIM)","volume":"32","author":"J Huisken","year":"2007","journal-title":"Opt Lett"},{"key":"ppat.1010399.ref079","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":"S Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ppat.1010399.ref080","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molbiopara.2016.11.005","article-title":"WormBase ParaSite\u2014a comprehensive resource for helminth genomics","volume":"215","author":"KL Howe","year":"2017","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1010399.ref081","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ppat.1010399.ref082","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nbt.3820","article-title":"Nextflow enables reproducible computational workflows","volume":"35","author":"P Di Tommaso","year":"2017","journal-title":"Nat Biotechnol"},{"key":"ppat.1010399.ref083","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":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"ppat.1010399.ref084","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/bioinformatics\/17.9.849","article-title":"The HMMTOP transmembrane topology prediction server","volume":"17","author":"GE Tusn\u00e1dy","year":"2001","journal-title":"Bioinformatics"},{"key":"ppat.1010399.ref085","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":"SF Altschul","year":"1990","journal-title":"J Mol Biol"},{"key":"ppat.1010399.ref086","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1186\/s12859-019-3019-7","article-title":"HH-suite3 for fast remote homology detection and deep protein annotation","volume":"20","author":"M Steinegger","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"ppat.1010399.ref087","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: improvements in performance and usability","volume":"30","author":"K Katoh","year":"2013","journal-title":"Mol Biol Evol"},{"key":"ppat.1010399.ref088","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1093\/bioinformatics\/btp348","article-title":"trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses","volume":"25","author":"S Capella-Guti\u00e9rrez","year":"2009","journal-title":"Bioinformatics"},{"key":"ppat.1010399.ref089","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies","volume":"32","author":"L-T Nguyen","year":"2014","journal-title":"Mol Biol Evol"},{"key":"ppat.1010399.ref090","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nmeth.4285","article-title":"ModelFinder: fast model selection for accurate phylogenetic estimates","volume":"14","author":"S Kalyaanamoorthy","year":"2017","journal-title":"Nat Methods"},{"key":"ppat.1010399.ref091","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/molbev\/msx281","article-title":"UFBoot2: Improving the Ultrafast Bootstrap Approximation","volume":"35","author":"DT Hoang","year":"2018","journal-title":"Mol Biol Evol"},{"key":"ppat.1010399.ref092","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1089\/10665270050514918","article-title":"Modeling amino acid replacement","volume":"7","author":"T M\u00fcller","year":"2000","journal-title":"J Comput Biol"},{"key":"ppat.1010399.ref093","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1093\/molbev\/mss140","article-title":"The influence of rate heterogeneity among sites on the time dependence of molecular rates","volume":"29","author":"J Soubrier","year":"2012","journal-title":"Mol Biol Evol"},{"key":"ppat.1010399.ref094","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.immuni.2018.10.016","article-title":"Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules","volume":"49","author":"RM Maizels","year":"2018","journal-title":"Immunity"},{"key":"ppat.1010399.ref095","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0166-6851(92)90094-Z","article-title":"Molecular characterization of a Dirofilaria immitis cDNA encoding a highly immunoreactive antigen","volume":"54","author":"J Culpepper","year":"1992","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1010399.ref096","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1128\/IAI.71.5.2422-2429.2003","article-title":"Parasite-specific immunomodulatory functions of filarial cystatin","volume":"71","author":"P Schierack","year":"2003","journal-title":"Infect Immun"},{"key":"ppat.1010399.ref097","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1756-3305-7-43","article-title":"Vaccination with recombinant Brugia malayi cystatin proteins alters worm migration, homing and final niche selection following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae","volume":"7","author":"S Arumugam","year":"2014","journal-title":"Parasit Vectors"},{"key":"ppat.1010399.ref098","doi-asserted-by":"crossref","first-page":"e1003930","DOI":"10.1371\/journal.ppat.1003930","article-title":"The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo","volume":"10","author":"JP Hewitson","year":"2014","journal-title":"PLoS Pathog"},{"key":"ppat.1010399.ref099","doi-asserted-by":"crossref","first-page":"7550","DOI":"10.1073\/pnas.95.13.7550","article-title":"Tropomyosin implicated in host protective responses to microfilariae in onchocerciasis","volume":"95","author":"RE Jenkins","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010399.ref100","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1021\/acsinfecdis.0c00565","article-title":"Immunization with Brugia malayi Calreticulin Protein Generates Robust Antiparasitic Immunity and Offers Protection during Experimental Lymphatic Filariasis","volume":"7","author":"S Yadav","year":"2021","journal-title":"ACS Infect Dis"},{"key":"ppat.1010399.ref101","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1007\/s00436-019-06316-8","article-title":"Troponin 1 of human filarial parasite Brugia malayi: cDNA cloning, expression, purification, and its immunoprophylactic potential","volume":"118","author":"V Kushwaha","year":"2019","journal-title":"Parasitol Res"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010399","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T19:39:05Z","timestamp":1675193945000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010399"}},"subtitle":[],"editor":[{"given":"Thomas B.","family":"Nutman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,4,7]]},"references-count":101,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010399","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.24.456436","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,7]]}}}