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While several computational methods have been developed to identify Kla sites, these approaches still suffer from small datasets. In this work, we collected 23\u00a0984 Kla sites in 7297 proteins from the literature to construct the benchmark dataset. Leveraging recent advances in feature encoding, we tailored a multi-feature hybrid system, which integrated eight complementary feature\u2013encoding strategies derived from two automated encoders and a composition-based module. Combining the hybrid system with deep learning, we presented our newly designed predictor named HybridKla, achieving an area under the curve (AUC) value of 0.8460. Compared to existing tools, HybridKla achieved &amp;gt;28.90% improvement of the AUC value (0.8460 versus 0.6563). we also conducted a proteome-wide search and provided a systematic prediction of Kla sites. The friendly online service of HybridKla is freely accessible for academic research at http:\/\/transkla.zzu.edu.cn\/.<\/jats:p>","DOI":"10.1093\/bib\/bbaf375","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T14:11:10Z","timestamp":1752502270000},"source":"Crossref","is-referenced-by-count":3,"title":["HybridKla: a hybrid deep learning framework for lactylation site prediction"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1410-7891","authenticated-orcid":false,"given":"Wanshan","family":"Ning","sequence":"first","affiliation":[{"name":"Institute for Clinical Medical Research, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University , Xiamen, Fujian 361003 ,","place":["China"]}]},{"given":"Feibo","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University , Zhengzhou, Henan 450001 ,","place":["China"]}]},{"given":"Ziwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University , Zhengzhou, Henan 450001 ,","place":["China"]}]},{"given":"Hang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University , Zhengzhou, Henan 450001 ,","place":["China"]}]},{"given":"Chentan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University , Zhengzhou, Henan 450001 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-363X","authenticated-orcid":false,"given":"Yaping","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University , Zhengzhou, Henan 450001 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