{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T18:04:26Z","timestamp":1774029866141,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council Discovery Project","doi-asserted-by":"publisher","award":["DP180103694"],"award-info":[{"award-number":["DP180103694"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council Discovery Project","doi-asserted-by":"publisher","award":["DP250103567"],"award-info":[{"award-number":["DP250103567"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuropeptides regulate diverse physiological and behavioural processes in parasites, yet their functional roles in the infective larval stages of Schistosoma mansoni remain poorly defined. In this study, we identified miracidia-derived putative neuropeptides and examined their roles in regulating miracidial behaviour. Peptidomic analysis revealed ten putative neuropeptides, including five whose proteomic identification in this life stage was previously unreported. Neuropeptide precursor proteins were evaluated for stage-specific expression and Schistosoma genus specificity to prioritise candidates with potential functional and biocontrol relevance. Protein\u2013protein interaction analysis identified Smp_176700 as a highly connected neuropeptide precursor associated with proteins implicated in miracidial structure and infection. Eight putative neuropeptides derived from six precursor proteins were synthesised and externally applied to miracidia in acute (1 min) and prolonged (360 min) behavioural assays. During acute exposure, most peptides induced significant concentration-dependent behavioural changes at 3 mg\/mL and 0.1 mg\/mL, characterised by reduced swimming velocity and increased directional change, with no significant effects at 0.01 mg\/mL. Prolonged exposure revealed peptide-specific effects, with ASLSYF-OH and FLLGLPPSLRQH-OH producing the most pronounced behavioural modulation. These findings demonstrate that S. mansoni miracidia express bioactive neuropeptides capable of modulating larval behaviour, providing insight into schistosome neurobiology and identifying potential targets for transmission-blocking interventions.<\/jats:p>","DOI":"10.3390\/ijms27062839","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:02:43Z","timestamp":1774026163000},"page":"2839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peptidomic Identification of Behaviour-Modulating Putative Neuropeptides in Schistosoma mansoni Miracidia"],"prefix":"10.3390","volume":"27","author":[{"given":"Conor E.","family":"Fogarty","sequence":"first","affiliation":[{"name":"Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"},{"name":"School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9129-2082","authenticated-orcid":false,"given":"Saowaros","family":"Suwansa-ard","sequence":"additional","affiliation":[{"name":"Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"},{"name":"School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1581-0283","authenticated-orcid":false,"given":"Tomas","family":"Lang","sequence":"additional","affiliation":[{"name":"Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"},{"name":"School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1551-4675","authenticated-orcid":false,"given":"Phong","family":"Phan","sequence":"additional","affiliation":[{"name":"Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary G.","family":"Duke","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-7588","authenticated-orcid":false,"given":"Russell C.","family":"Wyeth","sequence":"additional","affiliation":[{"name":"Department of Biology, St. Francis Xavier University, Antigonish, NS B2G2W5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-2076","authenticated-orcid":false,"given":"Scott F.","family":"Cummins","sequence":"additional","affiliation":[{"name":"Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"},{"name":"School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4876-7767","authenticated-orcid":false,"given":"Tianfang","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"},{"name":"School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Siddappa, N.B., Hemashettar, G., Shanmuganathan, V., Semenya, A.A., Sweeney, E.D., Paul, K.S., Lee, S.J., Secor, W.E., and Ruprecht, R.M. (2011). Schistosoma mansoni enhances host susceptibility to mucosal but not intravenous challenge by R5 Clade C SHIV. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001270"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/ijc.32538","article-title":"Cancer in Africa 2018: The role of infections","volume":"146","author":"Parkin","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"862","DOI":"10.4269\/ajtmh.2012.12-0248","article-title":"Mechanism of anemia in Schistosoma mansoni-infected school children in Western Kenya","volume":"87","author":"Butler","year":"2012","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_4","first-page":"153","article-title":"Schistosomiasis: Still a Cause of Significant Morbidity and Mortality","volume":"10","author":"Verjee","year":"2019","journal-title":"Res. Rep. Trop. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.5614\/j.math.fund.sci.2021.53.2.6","article-title":"The Role of Non-pharmacological Interventions on the Dynamics of Schistosomiasis","volume":"53","author":"Abokwara","year":"2021","journal-title":"J. Math. Fundam. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e54012","DOI":"10.7554\/eLife.54012","article-title":"Impact of community piped water coverage on re-infection with urogenital schistosomiasis in rural South Africa","volume":"9","author":"Mogeni","year":"2020","journal-title":"eLife"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8243","DOI":"10.1038\/s41598-022-11996-x","article-title":"Analysis of rhodopsin G protein-coupled receptor orthologs reveals semiochemical peptides for parasite (Schistosoma mansoni) and host (Biomphalaria glabrata) interplay","volume":"12","author":"Phan","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fogarty, C.E., Suwansa-Ard, S., Phan, P., McManus, D.P., Duke, M.G., Wyeth, R.C., Cummins, S.F., and Wang, T. (2022). Identification of Putative Neuropeptides That Alter the Behaviour of Schistosoma mansoni Cercariae. Biology, 11.","DOI":"10.3390\/biology11091344"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fogarty, C.E., Phan, P., Duke, M.G., McManus, D.P., Wyeth, R.C., Cummins, S.F., and Wang, T. (2022). Identification of Schistosoma mansoni miracidia attractant candidates in infected Biomphalaria glabrata using behaviour-guided comparative proteomics. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.954282"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/s13071-019-3708-0","article-title":"Comparative study of excretory-secretory proteins released by Schistosoma mansoni-resistant, susceptible and na\u00efve Biomphalaria glabrata","volume":"12","author":"Fogarty","year":"2019","journal-title":"Parasites Vectors"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, T., Wyeth, R.C., Liang, D., Bose, U., Ni, G., McManus, D.P., and Cummins, S.F. (2019). A Biomphalaria glabrata peptide that stimulates significant behaviour modifications in aquatic free-living Schistosoma mansoni miracidia. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0006948"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/s13071-017-2218-1","article-title":"Changes in the neuropeptide content of Biomphalaria ganglia nervous system following Schistosoma infection","volume":"10","author":"Wang","year":"2017","journal-title":"Parasites Vectors"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Phan, P., Fogarty, C.E., Eamens, A.L., Duke, M.G., McManus, D.P., Wang, T., and Cummins, S.F. (2024). ARGONAUTE2 Localizes to Sites of Sporocysts in the Schistosome-Infected Snail, Biomphalaria glabrata. Genes, 15.","DOI":"10.3390\/genes15081023"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ijpddr.2011.10.004","article-title":"Parasite neuropeptide biology: Seeding rational drug target selection?","volume":"2","author":"McVeigh","year":"2012","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lu, Z., Sp\u00e4nig, S., Weth, O., and Grevelding, C.G. (2019). Males, the Wrongly Neglected Partners of the Biologically Unprecedented Male-Female Interaction of Schistosomes. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00796"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ijpara.2016.05.007","article-title":"De novo discovery of neuropeptides in the genomes of parasitic flatworms using a novel comparative approach","volume":"46","author":"Koziol","year":"2016","journal-title":"Int. J. Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature08160","article-title":"The genome of the blood fluke Schistosoma mansoni","volume":"460","author":"Berriman","year":"2009","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.ijpara.2011.03.010","article-title":"Schistosome I\/Lamides\u2014A new family of bioactive helminth neuropeptides","volume":"41","author":"McVeigh","year":"2011","journal-title":"Int. J. Parasitol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1017\/S0031182019001756","article-title":"Towards deorphanizing G protein-coupled receptors of Schistosoma mansoni using the MALAR yeast two-hybrid system","volume":"147","author":"Weth","year":"2020","journal-title":"Parasitology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39880","DOI":"10.1074\/jbc.M405624200","article-title":"Structure and bioactivity of neuropeptide F from the human parasites Schistosoma mansoni and Schistosoma japonicum","volume":"279","author":"Humphries","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Collins, J.J., Hou, X., Romanova, E.V., Lambrus, B.G., Miller, C.M., Saberi, A., Sweedler, J.V., and Newmark, P.A. (2010). Genome-wide analyses reveal a role for peptide hormones in planarian germline development. PLoS Biol., 8, Correction in PLoS Biol. 2015, 13, e1002234. https:\/\/doi.org\/10.1371\/journal.pbio.1002234.","DOI":"10.1371\/journal.pbio.1002234"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1096\/fj.03-0429com","article-title":"A functionally atypical amidating enzyme from the human parasite Schistosoma mansoni","volume":"18","author":"Mair","year":"2004","journal-title":"FASEB J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.parint.2013.06.003","article-title":"Neurotransmitter transporters in schistosomes: Structure, function and prospects for drug discovery","volume":"62","author":"Ribeiro","year":"2013","journal-title":"Parasitol. Int."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gao, J., Yang, N., Lewis, F.A., Yau, P., Collins, J.J., Sweedler, J.V., and Newmark, P.A. (2019). A rotifer-derived paralytic compound prevents transmission of schistosomiasis to a mammalian host. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000485"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1186\/s13071-016-1837-2","article-title":"GPCR and IR genes in Schistosoma mansoni miracidia","volume":"9","author":"Liang","year":"2016","journal-title":"Parasites Vectors"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"You, J., Pan, F., Wang, S., Wang, Y., and Hu, Y. (2021). FMRFamide-Like Peptide 22 Influences the Head Movement, Host Finding, and Infection of Heterodera glycines. Front. Plant Sci., 12.","DOI":"10.3389\/fpls.2021.673354"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","unstructured":"Picard, M.A., Boissier, J., Roquis, D., Grunau, C., Allienne, J.F., Duval, D., Toulza, E., Arancibia, N., Caffrey, C.R., and Long, T. (2016). Sex-Biased Transcriptome of Schistosoma mansoni: Host-Parasite Interaction, Genetic Determinants and Epigenetic Regulators Are Associated with Sexual Differentiation. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004930"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2174\/1568026023393697","article-title":"Neuropeptide signaling systems\u2014Potential drug targets for parasite and pest control","volume":"2","author":"Maule","year":"2002","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/978-1-4419-6902-6_7","article-title":"Control of nematode parasites with agents acting on neuro-musculature systems: Lessons for neuropeptide ligand discovery","volume":"692","author":"Martin","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mach\u00e1\u010dek, T., Leontovy\u010d, R., \u0160m\u00eddov\u00e1, B., Majer, M., Vondr\u00e1\u010dek, O., Vojt\u011bchov\u00e1, I., Petr\u00e1sek, T., and Hor\u00e1k, P. (2022). Mechanisms of the host immune response and helminth-induced pathology during Trichobilharzia regenti (Schistosomatidae) neuroinvasion in mice. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010302"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Leontovy\u010d, R., Young, N.D., Korhonen, P.K., Hall, R.S., Tan, P., Mike\u0161, L., Ka\u0161n\u00fd, M., Hor\u00e1k, P., and Gasser, R.B. (2016). Comparative Transcriptomic Exploration Reveals Unique Molecular Adaptations of Neuropathogenic Trichobilharzia to Invade and Parasitize Its Avian Definitive Host. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004406"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"jeb151092","DOI":"10.1242\/jeb.151092","article-title":"Evolution of neuropeptide signalling systems","volume":"221","author":"Elphick","year":"2018","journal-title":"J. Exp. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e34473","DOI":"10.1016\/j.heliyon.2024.e34473","article-title":"Evolution of neuropeptide Y\/RFamide-like receptors in nematodes","volume":"10","author":"Reinhardt","year":"2024","journal-title":"Heliyon"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Peterkov\u00e1, K., Kone\u010dn\u00fd, L., Mach\u00e1\u010dek, T., Jedli\u010dkov\u00e1, L., Winkelmann, F., Sombetzki, M., and Dvo\u0159\u00e1k, J. (2024). Winners vs. losers: Schistosoma mansoni intestinal and liver eggs exhibit striking differences in gene expression and immunogenicity. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012268"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Willett, S., Olson, S.A., Horejsi, R.V., Nelson, C.N., and Wheeler, N.J. (2025). Tissue-Specific Distribution of Eggs in The Definitive Host Drives Transcriptomic and Behavioral Differences in Schistosoma mansoni Miracidia. bioRxiv.","DOI":"10.1101\/2025.08.15.670345"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17913","DOI":"10.1073\/pnas.1909710117","article-title":"Chemosensory mechanisms of host seeking and infectivity in skin-penetrating nematodes","volume":"117","author":"Gang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Morris, R., Wilson, L., Sturrock, M., Warnock, N.D., Carrizo, D., Cox, D., Maule, A.G., and Dalzell, J.J. (2017). A neuropeptide modulates sensory perception in the entomopathogenic nematode Steinernema carpocapsae. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006185"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100479","DOI":"10.1016\/j.mcpro.2022.100479","article-title":"Mass Spectrometry-Driven Discovery of Neuropeptides Mediating Nictation Behavior of Nematodes","volume":"22","author":"Cockx","year":"2023","journal-title":"Mol. Cell. Proteom."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, T., Zhao, M., Rotgans, B.A., Strong, A., Liang, D., Ni, G., Limpanont, Y., Ramasoota, P., McManus, D.P., and Cummins, S.F. (2016). Proteomic Analysis of the Schistosoma mansoni Miracidium. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147247"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chieu, H.D., Turner, L., Smith, M.K., Wang, T., Nocillado, J., Palma, P., Suwansa-Ard, S., Elizur, A., and Cummins, S.F. (2019). Aquaculture Breeding Enhancement: Maturation and Spawning in Sea Cucumbers Using a Recombinant Relaxin-Like Gonad-Stimulating Peptide. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00077"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/nbt.2377","article-title":"A cross-platform toolkit for mass spectrometry and proteomics","volume":"30","author":"Chambers","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/nmeth.1701","article-title":"SignalP 4.0: Discriminating signal peptides from transmembrane regions","volume":"8","author":"Petersen","year":"2011","journal-title":"Nat. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"W375","DOI":"10.1093\/nar\/gkh378","article-title":"PrediSi: Prediction of signal peptides and their cleavage positions","volume":"32","author":"Hiller","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","article-title":"Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes","volume":"305","author":"Krogh","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W267","DOI":"10.1093\/nar\/gkl161","article-title":"NeuroPred: A tool to predict cleavage sites in neuropeptide precursors and provide the masses of the resulting peptides","volume":"34","author":"Southey","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/bioinformatics\/16.2.135","article-title":"TEXshade: Shading and labeling of multiple sequence alignments using LATEX2 epsilon","volume":"16","author":"Beitz","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_51","first-page":"275","article-title":"The rapid generation of mutation data matrices from protein sequences","volume":"8","author":"Jones","year":"1992","journal-title":"Comput. Appl. Biosci."},{"key":"ref_52","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":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-1-60761-953-6_2","article-title":"Videograms: A method for repeatable unbiased quantitative behavioral analysis without scoring or tracking","volume":"51","author":"Wyeth","year":"2011","journal-title":"Neuromethods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ymeth.2016.09.016","article-title":"TrackMate: An open and extensible platform for single-particle tracking","volume":"115","author":"Tinevez","year":"2017","journal-title":"Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/B978-0-12-391857-4.00009-4","article-title":"Methods for cell and particle tracking","volume":"504","author":"Meijering","year":"2012","journal-title":"Methods Enzymol."},{"key":"ref_56","unstructured":"Kay, M., Elkin, L., Higgins, J., and Wobbrock, J. (2021, January 21). ARTool: Aligned Rank Transform for Nonparametric Factorial ANOVAs. Available online: https:\/\/github.com\/mjskay\/ARTool."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Elkin, L., Kay, M., Higgins, J., and Wobbrock, J. (2021, January 10\u201314). An Aligned Rank Transform Procedure for Multifactor Contrast Tests. Proceedings of the 34th Annual ACM Symposium on User Interface Software and Technology, Virtual.","DOI":"10.1145\/3472749.3474784"},{"key":"ref_58","unstructured":"R Core Team (RStudio: Integrated Development Environment for R, 2021). RStudio: Integrated Development Environment for R, version 4.1.0."},{"key":"ref_59","unstructured":"Wickham, H., and Bryan, J. (Readxl: Read Excel Files, 2019). Readxl: Read Excel Files, version 1.3.1."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the {tidyverse}","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"ref_61","unstructured":"Bache, S.M., and Wickham, H. (Magrittr: A Forward-Pipe Operator for R, 2020). Magrittr: A Forward-Pipe Operator for R, version 2.0.1."},{"key":"ref_62","unstructured":"Wickham, H. (Forcats: Tools for Working with Categorical Variables (Factors), 2021). Forcats: Tools for Working with Categorical Variables (Factors), version 0.5.1."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using {lme4}, version 1.1-27.1","volume":"67","author":"Bates","year":"2015","journal-title":"J. Stat. Softw."},{"key":"ref_64","unstructured":"Mazerolle, M.J. (AICcmodavg: Model Selection and Multimodel Inference Based on (Q)AIC(c), 2020). AICcmodavg: Model Selection and Multimodel Inference Based on (Q)AIC(c), version 2.3."},{"key":"ref_65","unstructured":"Fox, J., and Weisberg, S. (2019). An {R} Companion to Applied Regression, Sage."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/bimj.200810425","article-title":"Simultaneous Inference in General Parametric Models","volume":"50","author":"Hothorn","year":"2008","journal-title":"Biom. J."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_68","first-page":"8","article-title":"Plotrix: A package in the red light district of R","volume":"6","author":"Lemon","year":"2006","journal-title":"R-News"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1093\/bioinformatics\/btx364","article-title":"UpSetR: An R package for the visualization of intersecting sets and their properties","volume":"33","author":"Conway","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1021\/ct500592m","article-title":"Improved PEP-FOLD Approach for Peptide and Miniprotein Structure Prediction","volume":"10","author":"Shen","year":"2014","journal-title":"J. Chem. Theory Comput."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2839\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:03:16Z","timestamp":1774026196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":71,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062839"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062839","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}