{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:44:10Z","timestamp":1792266250585,"version":"4.4.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62473268"],"award-info":[{"award-number":["62473268"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62450002"],"award-info":[{"award-number":["62450002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62531002"],"award-info":[{"award-number":["62531002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62303328"],"award-info":[{"award-number":["62303328"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62373080"],"award-info":[{"award-number":["62373080"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Anti-inflammatory peptides (AIPs) show therapeutic potential for treating chronic and autoimmune diseases. Computational screening of these peptides remains challenging because their typically short sequences limit traditional feature extraction effectiveness, while homology-based methods incur high computational costs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This study proposes HD-AIP, an alignment-free heterogeneous dual-stream prediction architecture. This framework extracts peptide features in parallel from both macroscopic and microscopic perspectives. Macroscopically, HD-AIP integrates global semantic features extracted by two large protein language models, ProtT5 and ESM-2 3B, with sequence-level physicochemical properties, followed by feature selection and LightGBM classification. Microscopically, an asymmetric parallel network named CT-Net utilizes BioVec embeddings and residue-level physicochemical features, using a CNN branch to capture local motifs and a Transformer branch to model long-range dependencies. The two streams are adaptively fused via a dynamic soft ensemble strategy. On an independent test set, HD-AIP outperforms baseline models across multiple metrics including accuracy, area under the receiver operating characteristic curve, and the Matthews correlation coefficient. These results indicate that HD-AIP improves AIP prediction performance without sequence alignment. This architecture serves as an effective computational tool for the high-throughput virtual screening and candidate discovery of AIPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>You can find the source code and dataset needed on GitHub (https:\/\/github.com\/Zerofly0\/HD-AIP). The required package files have been listed in the readme.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag697","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:28:36Z","timestamp":1789756116000},"source":"Crossref","is-referenced-by-count":0,"title":["HD-AIP: a heterogeneous dual-stream alignment-free framework for anti-inflammatory peptide prediction based on language models and CT-Net"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4198-1951","authenticated-orcid":false,"given":"Jiangli","family":"Li","sequence":"first","affiliation":[{"name":"University of Electronic Science and Technology of China School of Computer Science and Engineering (School of Cyber Security), , Chengdu, Sichuan 611731,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6406-1142","authenticated-orcid":false,"given":"Quan","family":"Zou","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China Institute of Fundamental and Frontier Sciences, , Chengdu, Sichuan 610054,","place":["China"]},{"name":"University of Electronic Science and Technology of China Yangtze Delta Region Institute (Quzhou), , Quzhou, Zhejiang 324003,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3408-5375","authenticated-orcid":false,"given":"Yansu","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China Institute of Fundamental and Frontier Sciences, , Chengdu, Sichuan 610054,","place":["China"]},{"name":"University of Electronic Science and Technology of China Yangtze Delta Region Institute (Quzhou), , Quzhou, Zhejiang 324003,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifeng","family":"Bai","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China Department of Oncology Sichuan Provincial People\u2019s Hospital, , Chengdu, Sichuan 610072,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhou","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China Department of Stomotology Sichuan Provincial People\u2019s Hospital, , Chengdu, Sichuan 610072,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9175-4649","authenticated-orcid":false,"given":"Mengting","family":"Niu","sequence":"additional","affiliation":[{"name":"Shenzhen Polytechnic University School of Electronic and Communication Engineering, , Shenzhen, Guangdong 518055,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026101714572153800_btag697-B1","doi-asserted-by":"publisher","first-page":"9609","DOI":"10.1021\/acs.jcim.4c01758","article-title":"DeepAIPs-Pred: predicting anti-inflammatory peptides using local evolutionary transformation images and structural embedding-based optimal descriptors with self-normalized BiTCNs","volume":"64","author":"Akbar","year":"2024","journal-title":"J Chem Inf Model"},{"key":"2026101714572153800_btag697-B2","doi-asserted-by":"publisher","first-page":"35747","DOI":"10.1021\/acsomega.5c02422","article-title":"DeepAIPs-SFLA: deep convolutional model for prediction of anti-inflammatory peptides using binary pattern decomposition of novel multiview descriptors with an SFLA approach","volume":"10","author":"Akbar","year":"2025","journal-title":"ACS Omega"},{"key":"2026101714572153800_btag697-B3","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"2026101714572153800_btag697-B4","doi-asserted-by":"publisher","first-page":"e0141287","DOI":"10.1371\/journal.pone.0141287","article-title":"Continuous distributed representation of biological sequences for deep proteomics and genomics","volume":"10","author":"Asgari","year":"2015","journal-title":"PLoS One"},{"key":"2026101714572153800_btag697-B5","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1053\/j.gastro.2017.10.049","article-title":"Mechanisms of damage to the gastrointestinal tract from nonsteroidal anti-inflammatory drugs","volume":"154","author":"Bjarnason","year":"2018","journal-title":"Gastroenterology"},{"key":"2026101714572153800_btag697-B6","first-page":"785","author":"Chen"},{"key":"2026101714572153800_btag697-B7","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/299371a0","article-title":"The helical hydrophobic moment: a measure of the amphiphilicity of a helix","volume":"299","author":"Eisenberg","year":"1982","journal-title":"Nature"},{"key":"2026101714572153800_btag697-B8","doi-asserted-by":"publisher","first-page":"7112","DOI":"10.1109\/TPAMI.2021.3095381","article-title":"ProtTrans: toward understanding the language of life through self-supervised learning","volume":"44","author":"Elnaggar","year":"2022","journal-title":"IEEE Trans Pattern Anal Mach Intell"},{"key":"2026101714572153800_btag697-B9","doi-asserted-by":"publisher","first-page":"7886","DOI":"10.1021\/acs.jcim.3c01602","article-title":"Predicting anti-inflammatory peptides by ensemble machine learning and deep learning","volume":"63","author":"Guan","year":"2023","journal-title":"J Chem Inf Model"},{"key":"2026101714572153800_btag697-B10","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1038\/s42003-024-06911-1","article-title":"PepNet: an interpretable neural network for anti-inflammatory and antimicrobial peptides prediction using a pre-trained protein language model","volume":"7","author":"Han","year":"2024","journal-title":"Commun Biol"},{"key":"2026101714572153800_btag697-B11","first-page":"770","author":"He"},{"key":"2026101714572153800_btag697-B12","doi-asserted-by":"publisher","first-page":"D202","DOI":"10.1093\/nar\/gkm998","article-title":"AAindex: amino acid index database, progress report 2008","volume":"36","author":"Kawashima","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2026101714572153800_btag697-B13","first-page":"3146","article-title":"Lightgbm: a highly efficient gradient boosting decision tree","volume":"30","author":"Ke","year":"2017","journal-title":"Adv Neural Inf Process Syst"},{"key":"2026101714572153800_btag697-B14","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fgene.2019.00129","article-title":"PreAIP: computational prediction of anti-inflammatory peptides by integrating multiple complementary features","volume":"10","author":"Khatun","year":"2019","journal-title":"Front Genet"},{"key":"2026101714572153800_btag697-B15","first-page":"1746","author":"Kim"},{"key":"2026101714572153800_btag697-B16","author":"Lin"},{"key":"2026101714572153800_btag697-B17","doi-asserted-by":"publisher","first-page":"170105","DOI":"10.1007\/s11432-024-4485-0","article-title":"From intention to implementation: automating biomedical research via LLMs","volume":"68","author":"Luo","year":"2025","journal-title":"Sci China Inf Sci"},{"key":"2026101714572153800_btag697-B18","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3389\/fphar.2018.00276","article-title":"AIPpred: sequence-based prediction of anti-inflammatory peptides using random forest","volume":"9","author":"Manavalan","year":"2018","journal-title":"Front Pharmacol"},{"key":"2026101714572153800_btag697-B19","author":"Miyato"},{"key":"2026101714572153800_btag697-B20","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.cell.2010.02.029","article-title":"Nonresolving inflammation","volume":"140","author":"Nathan","year":"2010","journal-title":"Cell"},{"key":"2026101714572153800_btag697-B21","doi-asserted-by":"publisher","first-page":"194904","DOI":"10.1007\/s11704-024-40060-2","article-title":"Computational approaches for circRNA-disease association prediction: a review","volume":"19","author":"Niu","year":"2025","journal-title":"Front Comput Sci"},{"key":"2026101714572153800_btag697-B22","doi-asserted-by":"publisher","first-page":"e2016239118","DOI":"10.1073\/pnas.2016239118","article-title":"Biological structure and function emerge from scaling unsupervised learning to 250 million protein sequences","volume":"118","author":"Rives","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026101714572153800_btag697-B23","author":"Vaswani"},{"key":"2026101714572153800_btag697-B24","doi-asserted-by":"publisher","first-page":"D339","DOI":"10.1093\/nar\/gky1006","article-title":"The immune epitope database (IEDB): 2018 update","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2026101714572153800_btag697-B25","doi-asserted-by":"publisher","first-page":"212106","DOI":"10.1007\/s11432-024-4171-9","article-title":"SBSM-Pro: support bio-sequence machine for proteins","volume":"67","author":"Wang","year":"2024","journal-title":"Sci China Inf Sci"},{"key":"2026101714572153800_btag697-B26","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0893-6080(05)80023-1","article-title":"Stacked generalization","volume":"5","author":"Wolpert","year":"1992","journal-title":"Neural Netw"},{"key":"2026101714572153800_btag697-B27","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/s12915-025-02314-8","article-title":"NeXtMD: a new generation of machine learning and deep learning stacked hybrid framework for accurate identification of anti-inflammatory peptides","volume":"23","author":"Xie","year":"2025","journal-title":"BMC Biol"},{"key":"2026101714572153800_btag697-B28","doi-asserted-by":"publisher","first-page":"e32951","DOI":"10.1016\/j.heliyon.2024.e32951","article-title":"A BERT-based approach for identifying anti-inflammatory peptides using sequence information","volume":"10","author":"Xu","year":"2024","journal-title":"Heliyon"},{"key":"2026101714572153800_btag697-B29","doi-asserted-by":"publisher","first-page":"3982","DOI":"10.1093\/bioinformatics\/btaa275","article-title":"PPTPP: a novel therapeutic peptide prediction method using physicochemical property encoding and adaptive feature representation learning","volume":"36","author":"Zhang","year":"2020","journal-title":"Bioinformatics"},{"key":"2026101714572153800_btag697-B30","doi-asserted-by":"publisher","first-page":"773202","DOI":"10.3389\/fgene.2021.773202","article-title":"iAIPs: identifying anti-inflammatory peptides using random forest","volume":"12","author":"Zhao","year":"2021","journal-title":"Front Genet"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btag697\/71276884\/btag697.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/42\/10\/btag697\/71276884\/btag697.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/42\/10\/btag697\/71276884\/btag697.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:57:32Z","timestamp":1792263452000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btag697\/8823707"}},"subtitle":[],"editor":[{"given":"Daisuke","family":"Kihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btag697","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,9,21]]},"article-number":"btag697"}}