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Given a relatively limited amount of experimental data, developing accurate sequence-based predictors of substrate cleavage sites facilitates a better understanding of protease functions and substrate specificity. While many protease-specific predictors of substrate cleavage sites were developed, these efforts are outpaced by the growth of the protease substrate cleavage data. In particular, since data for 100+ protease types are available and this number continues to grow, it becomes impractical to publish predictors for new protease types, and instead it might be better to provide a computational platform that helps users to quickly and efficiently build predictors that address their specific needs. To this end, we conceptualized, developed, tested and released a versatile bioinformatics platform, ProsperousPlus, that empowers users, even those with no programming or little bioinformatics background, to build fast and accurate predictors of substrate cleavage sites. ProsperousPlus facilitates the use of the rapidly accumulating substrate cleavage data to train, empirically assess and deploy predictive models for user-selected substrate types. Benchmarking tests on test datasets show that our platform produces predictors that on average exceed the predictive performance of current state-of-the-art approaches. ProsperousPlus is available as a webserver and a stand-alone software package at http:\/\/prosperousplus.unimelb-biotools.cloud.edu.au\/.<\/jats:p>","DOI":"10.1093\/bib\/bbad372","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T19:32:48Z","timestamp":1698175968000},"source":"Crossref","is-referenced-by-count":29,"title":["<i>ProsperousPlus<\/i>: a one-stop and comprehensive platform for accurate protease-specific substrate cleavage prediction and machine-learning model construction"],"prefix":"10.1093","volume":"24","author":[{"given":"Fuyi","family":"Li","sequence":"first","affiliation":[{"name":"College of Information Engineering, Northwest A&F University , Shaanxi 712100 , China"},{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI) , Faculty of Health and Medical Sciences, , Adelaide, SA 5005 , Australia"},{"name":"The University of Adelaide , Faculty of Health and Medical Sciences, , Adelaide, SA 5005 , Australia"},{"name":"The Peter Doherty Institute for Infection and Immunity, The University of Melbourne , VIC 3000 , Australia"}]},{"given":"Cong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Information Engineering, Northwest A&F University , Shaanxi 712100 , China"}]},{"given":"Xudong","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Information Engineering, Northwest A&F University , Shaanxi 712100 , China"}]},{"given":"Tatsuya","family":"Akutsu","sequence":"additional","affiliation":[{"name":"Bioinformatics Center , Institute for Chemical Research, , Kyoto 611-0011 , Japan"},{"name":"Kyoto University , Institute for Chemical Research, , Kyoto 611-0011 , Japan"}]},{"given":"Geoffrey I","family":"Webb","sequence":"additional","affiliation":[{"name":"Monash Data Futures Institute, Monash University , VIC 3800 , Australia"}]},{"given":"Lachlan J M","family":"Coin","sequence":"additional","affiliation":[{"name":"The Peter Doherty Institute for Infection and Immunity, The University of Melbourne , VIC 3000 , Australia"}]},{"given":"Lukasz","family":"Kurgan","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Virginia Commonwealth University , Richmond, VA 23284 , USA"}]},{"given":"Jiangning","family":"Song","sequence":"additional","affiliation":[{"name":"Monash Data Futures Institute, Monash University , VIC 3800 , Australia"},{"name":"Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University , VIC 3800 , Australia"}]}],"member":"286","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"2023102418065475700_ref1","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/nrc2228","article-title":"Emerging roles of proteases in tumour suppression","volume":"7","author":"Lopez-Otin","year":"2007","journal-title":"Nat Rev 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