{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T12:39:03Z","timestamp":1762605543801},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The production of neuropeptides from their precursor proteins is the result of a complex series of enzymatic processing steps. Often, the annotation of new neuropeptide genes from sequence information outstrips biochemical assays and so bioinformatics tools can provide rapid information on the most likely peptides produced by a gene. Predicting the final bioactive neuropeptides from precursor proteins requires accurate algorithms to determine which locations in the protein are cleaved.<\/jats:p>\n               <jats:p>Results: Predictive models were trained on Apis mellifera and Drosophila melanogaster precursors using binary logistic regression, multi-layer perceptron and k-nearest neighbor models. The final predictive models included specific amino acids at locations relative to the cleavage sites. Correct classification rates ranged from 78 to 100% indicating that the models adequately predicted cleaved and non-cleaved positions across a wide range of neuropeptide families and insect species. The model trained on D.melanogaster data had better generalization properties than the model trained on A. mellifera for the data sets considered. The reliable and consistent performance of the models in the test data sets suggests that the bioinformatics strategies proposed here can accurately predict neuropeptides in insects with sequence information based on neuropeptides with biochemical and sequence information in well-studied species.<\/jats:p>\n               <jats:p>Contact: \u00a0rodrgzzs@uiuc.edu<\/jats:p>\n               <jats:p>Supplementary information: Sequences and cleavage information are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn044","type":"journal-article","created":{"date-parts":[[2008,2,6]],"date-time":"2008-02-06T01:25:52Z","timestamp":1202261152000},"page":"815-825","source":"Crossref","is-referenced-by-count":61,"title":["Prediction of neuropeptide cleavage sites in insects"],"prefix":"10.1093","volume":"24","author":[{"given":"Bruce R.","family":"Southey","sequence":"first","affiliation":[{"name":"1 Department of Chemistry and 2Department of Animal Sciences, University of Illinois, Urbana, IL, USA"},{"name":"1 Department of Chemistry and 2Department of Animal Sciences, University of Illinois, Urbana, IL, USA"}]},{"given":"Jonathan V.","family":"Sweedler","sequence":"additional","affiliation":[{"name":"1 Department of Chemistry and 2Department of Animal Sciences, University of Illinois, Urbana, IL, USA"}]},{"given":"Sandra L.","family":"Rodriguez-Zas","sequence":"additional","affiliation":[{"name":"1 Department of Chemistry and 2Department of Animal Sciences, University of Illinois, Urbana, IL, USA"}]}],"member":"286","published-online":{"date-parts":[[2008,2,5]]},"reference":[{"key":"2023020209511496900_B1","volume-title":"An Introduction to Categorical Data Analysis.","author":"Agresti","year":"1996"},{"key":"2023020209511496900_B2","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.peptides.2007.04.014","article-title":"Neuropeptide precursors in Tribolium castaneum","volume":"28","author":"Amare","year":"2007","journal-title":"Peptides"},{"key":"2023020209511496900_B3","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1021\/pr0504541","article-title":"Bridging neuropeptidomics and genomics with bioinformatics: prediction of mammalian neuropeptide prohormone processing","volume":"5","author":"Amare","year":"2006","journal-title":"J. Proteome Res"},{"key":"2023020209511496900_B4","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/jms.744","article-title":"Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two-dimensional capillary liquid chromatography quadrupole time-of-flight mass spectrometry","volume":"40","author":"Baggerman","year":"2005","journal-title":"J. Mass Spectrom"},{"key":"2023020209511496900_B5","doi-asserted-by":"crossref","first-page":"40368","DOI":"10.1074\/jbc.M206257200","article-title":"Peptidomics of the larval Drosophila melanogaster central nervous system","volume":"277","author":"Baggerman","year":"2002","journal-title":"J. Biol. Chem"},{"key":"2023020209511496900_B6","doi-asserted-by":"crossref","first-page":"D154","DOI":"10.1093\/nar\/gki070","article-title":"The universal protein resource (UniProt)","volume":"33","author":"Bairoch","year":"2005","journal-title":"Nucl. Acids Res"},{"key":"2023020209511496900_B7","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/bioinformatics\/16.5.412","article-title":"Assessing the accuracy of prediction algorithms for classification: an overview","volume":"16","author":"Baldi","year":"2000","journal-title":"Bioinformatics"},{"key":"2023020209511496900_B8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.jmb.2004.05.028","article-title":"Improved prediction of signal peptides: SignalP 3.0","volume":"340","author":"Bendtsen","year":"2004","journal-title":"J. Mol. Biol"},{"key":"2023020209511496900_B9","first-page":"291","article-title":"The enzymology of PC1 and PC2","volume-title":"The Enzymes Volume XXII.","author":"Cameron","year":"2001"},{"key":"2023020209511496900_B10","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1109\/81.596943","article-title":"On neural-network implementations of k-nearest neighbor pattern classifiers","volume":"44","author":"Chen","year":"1997","journal-title":"IEEE Trans. circuits and Syst.\u2014I: Fundam. Theory Appl"},{"key":"2023020209511496900_B11","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/S0965-1748(98)00065-4","article-title":"Isolation and identification of the cDNA encoding the pheromone biosynthesis activating neuropeptide and additional neuropeptides in the oriental tobacco budworm, Helicoverpa assulta (Lepidoptera: Noctuidae)","volume":"28","author":"Choi","year":"1998","journal-title":"Insect Biochem. Mol. Biol"},{"key":"2023020209511496900_B12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0014-5793(91)80290-J","article-title":"Consensus sequence for processing of peptide precursors at monobasic sites","volume":"280","author":"Devi","year":"1991","journal-title":"FEBS Lett"},{"key":"2023020209511496900_B13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/protein\/gzh013","article-title":"Prediction of proprotein convertase cleavage sites","volume":"17","author":"Duckert","year":"2004","journal-title":"Protein Eng. Des. Sel"},{"key":"2023020209511496900_B14","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0965-1748(98)00033-2","article-title":"The pheromone biosynthesis activating neuropeptide (PBAN) of the black cutworm moth, Agrotis ipsilon: immunohistochemistry, molecular characterization and bioassay of its peptide sequence","volume":"28","author":"Duportets","year":"1998","journal-title":"Insect Biochem. Mol. Biol"},{"key":"2023020209511496900_B15","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.peptides.2005.06.029","article-title":"Structural studies of Drosophila short neuropeptide F: occurrence and receptor binding activity","volume":"27","author":"Garczynski","year":"2006","journal-title":"Peptides"},{"key":"2023020209511496900_B16","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-21606-5","volume-title":"The Elements of Statistical Learning: Data Mining, Inference, and Prediction with 200 Full-color Illustrations.","author":"Hastie","year":"2001"},{"key":"2023020209511496900_B17","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nsb941","article-title":"The crystal structure of the proprotein processing proteinase furin explains its stringent specificity","volume":"10","author":"Henrich","year":"2003","journal-title":"Nat. Struct. Biol"},{"key":"2023020209511496900_B18","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1021\/bi034434t","article-title":"2.4 A resolution crystal structure of the prototypical hormone-processing protease Kex2 in complex with an Ala-Lys-Arg boronic acid inhibitor","volume":"42","author":"Holyoak","year":"2003","journal-title":"Biochemistry"},{"key":"2023020209511496900_B19","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nature05260","article-title":"Insights into social insects from the genome of the honeybee Apis mellifera","volume":"443","author":"Honeybee Genome Sequencing Consortium","year":"2006","journal-title":"Nature"},{"key":"2023020209511496900_B20","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1515\/BC.2006.179","article-title":"Unique neuronal functions of cathepsin L and cathepsin B in secretory vesicles: biosynthesis of peptides in neurotransmission and neurodegenerative disease","volume":"387","author":"Hook","year":"2006","journal-title":"Biol.Chem"},{"key":"2023020209511496900_B21","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/mas.20055","article-title":"Discovering new invertebrate neuropeptides using mass spectrometry","volume":"25","author":"Hummon","year":"2006","journal-title":"Mass Spectrom. Rev"},{"key":"2023020209511496900_B22","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1126\/science.1124128","article-title":"From the genome to the proteome: uncovering peptides in the Apis brain","volume":"314","author":"Hummon","year":"2006","journal-title":"Science"},{"key":"2023020209511496900_B23","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1021\/pr034046d","article-title":"From precursor to final peptides: a statistical sequence-based approach to predicting prohormone processing","volume":"2","author":"Hummon","year":"2003","journal-title":"J. Proteome Res"},{"key":"2023020209511496900_B24","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0965-1748(98)00017-4","article-title":"cDNA cloning and sequence determination of the pheromone biosynthesis activating neuropeptide of Mamestra brassicae: a new member of the PBAN family","volume":"28","author":"Jacquin-Joly","year":"1998","journal-title":"Insect Biochem. Mol. Biol"},{"key":"2023020209511496900_B25","volume-title":"Principles of neural science.","author":"Kandel","year":"2000"},{"key":"2023020209511496900_B26","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1074\/mcp.M400114-MCP200","article-title":"In silico identification of new secretory peptide genes in Drosophila melanogaster","volume":"5","author":"Liu","year":"2006","journal-title":"Mol. Cell. Proteomics"},{"key":"2023020209511496900_B27","doi-asserted-by":"crossref","first-page":"6506","DOI":"10.1073\/pnas.91.14.6506","article-title":"Structural organization of the Helicoverpa zea gene encoding the precursor protein for pheromone biosynthesis-activating neuropeptide and other neuropeptides","volume":"91","author":"Ma","year":"1994","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020209511496900_B28","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/0005-2795(75)90109-9","article-title":"Comparison of the predicted and observed secondary structure of T4 phage lysozyme","volume":"405","author":"Matthews","year":"1975","journal-title":"Biochim. Biophys. Acta"},{"key":"2023020209511496900_B29","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1101\/gr.5755407","article-title":"Identification of novel peptide hormones in the human proteome by hidden Markov model screening","volume":"17","author":"Mirabeau","year":"2007","journal-title":"Genome Res"},{"key":"2023020209511496900_B30","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.patrec.2006.10.012","article-title":"Ensemblator: An ensemble of classifiers for reliable classification of biological data","volume":"28","author":"Nanni","year":"2007","journal-title":"Pattern Recognit. Lett"},{"key":"2023020209511496900_B31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0301-0082(02)00057-6","article-title":"Neuropeptides in the nervous system of Drosophila and other insects: multiple roles as neuromodulators and neurohormones","volume":"68","author":"Nassel","year":"2002","journal-title":"Prog. Neurobiol"},{"key":"2023020209511496900_B32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0933-3657(03)00050-2","article-title":"WeAidU\u2014a decision support system for myocardial perfusion images using multi-layer perceptron neural networks","volume":"30","author":"Ohlsson","year":"2004","journal-title":"Artif. Intell. Med"},{"key":"2023020209511496900_B33","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1111\/j.1460-9568.2004.03598.x","article-title":"Unique accumulation of neuropeptides in an insect: FMRFamide-related peptides in the cockroach, Periplaneta americana","volume":"20","author":"Predel","year":"2004","journal-title":"Eur. J. Neurosci"},{"key":"2023020209511496900_B34","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/cne.20145","article-title":"Peptidomics of CNS-associated neurohemal systems of adult Drosophila melanogaster: a mass spectrometric survey of peptides from individual flies","volume":"474","author":"Predel","year":"2004","journal-title":"J. Comp. Neurol"},{"key":"2023020209511496900_B35","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1111\/j.1432-1033.1995.tb20192.x","article-title":"Role of amino acid sequences flanking dibasic cleavage sites in precursor proteolytic processing. The importance of the first residue C-terminal of the cleavage site","volume":"227","author":"Rholam","year":"1995","journal-title":"Eur. J. Biochem"},{"key":"2023020209511496900_B36","doi-asserted-by":"crossref","first-page":"4525","DOI":"10.1021\/cr010168i","article-title":"Precursor processing by kex2\/furin proteases","volume":"102","author":"Rockwell","year":"2002","journal-title":"Chem. Rev"},{"key":"2023020209511496900_B37","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1073\/pnas.90.8.3251","article-title":"Precursor polyprotein for multiple neuropeptides secreted from the suboesophageal ganglion of the silkworm Bombyx mori: characterization of the cDNA encoding the diapause hormone precursor and identification of additional peptides","volume":"90","author":"Sato","year":"1993","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020209511496900_B38","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0006-291X(67)80055-X","article-title":"On the size of the active site in proteases. I. Papain","volume":"27","author":"Schechter","year":"1967","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023020209511496900_B39","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/0167-9473(95)00032-1","article-title":"Neural networks and logistic regression: Part I","volume":"21","author":"Schumacher","year":"1996","journal-title":"Comp. Stat. Data Anal"},{"key":"2023020209511496900_B40","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1042\/bse0380079","article-title":"Precursor convertases in the secretory pathway, cytosol and extracellular milieu","volume":"38","author":"Seidah","year":"2002","journal-title":"Essays Biochem"},{"key":"2023020209511496900_B41","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":"Nucl. Acids Res"},{"key":"2023020209511496900_B42","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.peptides.2005.07.026","article-title":"Prediction of neuropeptide prohormone cleavages with application to RFamides","volume":"27","author":"Southey","year":"2006","journal-title":"Peptides"},{"key":"2023020209511496900_B43","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/0167-9473(95)00033-X","article-title":"Neural networks and logistic regression: Part II","volume":"21","author":"Vach","year":"1996","journal-title":"Comp. Stat. Data Anal"},{"key":"2023020209511496900_B44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/(SICI)1520-6327(200002)43:2<49::AID-ARCH1>3.0.CO;2-M","article-title":"Mono- and dibasic proteolytic cleavage sites in insect neuroendocrine peptide precursors","volume":"43","author":"Veenstra","year":"2000","journal-title":"Arch. Insect Biochem. Physiol"},{"key":"2023020209511496900_B45","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1111\/j.1471-4159.2005.03634.x","article-title":"Direct mass spectrometric peptide profiling and fragmentation of larval peptide hormone release sites in Drosophila melanogaster reveals tagma-specific peptide expression and differential processing","volume":"96","author":"Wegener","year":"2006","journal-title":"J. Neurochem"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/6\/815\/49045685\/bioinformatics_24_6_815.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/6\/815\/49045685\/bioinformatics_24_6_815.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T10:46:08Z","timestamp":1675334768000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/6\/815\/194519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,5]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn044","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,3,15]]},"published":{"date-parts":[[2008,2,5]]}}}