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Gram-positive bacteria can secrete proteins through multiple secretion pathways. The non-classical secretion pathway has recently received increasing attention among these secretion pathways, but its exact mechanism remains unclear. Non-classical secreted proteins (NCSPs) are a class of secreted proteins lacking signal peptides and motifs. Several NCSP predictors have been proposed to identify NCSPs and most of them employed the whole amino acid sequence of NCSPs to construct the model. However, the sequence length of different proteins varies greatly. In addition, not all regions of the protein are equally important and some local regions are not relevant to the secretion. The functional regions of the protein, particularly in the N- and C-terminal regions, contain important determinants for secretion. In this study, we propose a new hybrid deep learning-based framework, referred to as ASPIRER, which improves the prediction of NCSPs from amino acid sequences. More specifically, it combines a whole sequence-based XGBoost model and an N-terminal sequence-based convolutional neural network model; 5-fold cross-validation and independent tests demonstrate that ASPIRER achieves superior performance than existing state-of-the-art approaches. The source code and curated datasets of ASPIRER are publicly available at https:\/\/github.com\/yanwu20\/ASPIRER\/. ASPIRER is anticipated to be a useful tool for improved prediction of novel putative NCSPs from sequences information and prioritization of candidate proteins for follow-up experimental validation.<\/jats:p>","DOI":"10.1093\/bib\/bbac031","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T12:08:37Z","timestamp":1643112517000},"source":"Crossref","is-referenced-by-count":21,"title":["ASPIRER: a new computational approach for identifying non-classical secreted proteins based on deep learning"],"prefix":"10.1093","volume":"23","author":[{"given":"Xiaoyu","family":"Wang","sequence":"first","affiliation":[{"name":"Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology , Monash University, Melbourne, VIC 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology , The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology , Monash University, Melbourne, VIC 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Data Science and AI , Faculty of Information Technology, Monash University, Melbourne, VIC 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey I","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Data Science and AI , Faculty of Information Technology, Monash University, Melbourne, VIC 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongyuan","family":"Ge","sequence":"additional","affiliation":[{"name":"Monash e-Research Centre and Faculty of Engineering , Monash University, Melbourne, VIC 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute and Department of Microbiology , Monash University, Melbourne, VIC 3800 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8031-9086","authenticated-orcid":false,"given":"Jiangning","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Data Science and AI , Faculty of Information Technology, Monash University, Melbourne, VIC 3800 , 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