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Five years ago, we introduced PhaLP, a centralized resource for Phage Lytic Protein sequences and associated metadata to support global research efforts. Here, we present PhaLP 2.0, an enhanced database designed to address key challenges in computational lysin research by integrating newly identified lysins from thousands of metagenomes. To expand the known diversity of lysins beyond that of cultured phages, we developed SUBLYME, a protein-embedding-based machine-learning Software designed to Uncover and classify Bacteriophage Lysins from Metagenomic datasets. Using embeddings derived from the well-curated sequences of the original PhaLP database, we trained support vector machines to distinguish lysins from non-lysins in viromes and classify them as endolysins or virion-associated lysins. The models achieved an average F1 score of 98% on held-out clusters. SUBLYME enabled the discovery of 743\u2009000 new lysin sequences from EnVhogDB, a virome-derived protein database, increasing the number of known lysin clusters 40-fold, from 1000 to 40\u2009000. SUBLYME and PhaLP 2.0 are accessible online at https:\/\/github.com\/Rousseau-Team\/sublyme and https:\/\/phalp.ugent.be, respectively. Together, these advances establish PhaLP 2.0 as a comprehensive and scalable portal for lysin discovery, classification, and sequence analysis, paving the way for future antibacterial applications and evolutionary insights.<\/jats:p>","DOI":"10.1093\/database\/baag033","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:42:54Z","timestamp":1779968574000},"source":"Crossref","is-referenced-by-count":0,"title":["PhaLP 2.0: extending the community-oriented phage lysin database with a SUBLYME pipeline for metagenomic discovery"],"prefix":"10.1093","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5796-8598","authenticated-orcid":false,"given":"Alexandre","family":"Boulay","sequence":"first","affiliation":[{"name":"D\u00e9partement de biochimie, de microbiologie et de bio-informatique, Universit\u00e9 Laval , 1045 avenue de la M\u00e9decine, Qu\u00e9bec, Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre Nutrition, Sant\u00e9 et Soci\u00e9t\u00e9 (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Universit\u00e9 Laval , 2440 Bd Hochelaga Suite 1710, Qu\u00e9bec, Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Department of Biotechnology, Ghent University, Valentin Vaerwyckweg 1 , Ghent 9000 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"N\u00e9meth","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Ghent University, Valentin Vaerwyckweg 1 , Ghent 9000 ,","place":["Belgium"]},{"name":"KERMIT, Department of Data Analysis and Mathematical Modelling, Ghent University, Coupure links 653, Ghent 9000,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Criel","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Ghent University, Valentin Vaerwyckweg 1 , Ghent 9000 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-6061","authenticated-orcid":false,"given":"Michiel","family":"Stock","sequence":"additional","affiliation":[{"name":"KERMIT, Department of Data Analysis and Mathematical Modelling, Ghent University, Coupure links 653, Ghent 9000,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"De\u00a0Baets","sequence":"additional","affiliation":[{"name":"KERMIT, Department of Data Analysis and Mathematical Modelling, Ghent University, Coupure links 653, Ghent 9000,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0560-6023","authenticated-orcid":false,"given":"Clovis","family":"Galiez","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CNRS, Grenoble INP , LJK, 38000 Grenoble ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-6024","authenticated-orcid":false,"given":"Elsa","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Centre Nutrition, Sant\u00e9 et Soci\u00e9t\u00e9 (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Universit\u00e9 Laval , 2440 Bd Hochelaga Suite 1710, Qu\u00e9bec, Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"D\u00e9partement d\u2019informatique et de g\u00e9nie logiciel, Universit\u00e9 Laval , 1045 avenue de la M\u00e9decine, Qu\u00e9bec, Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Centre de Recherche en Donn\u00e9es Massives (CRDM) de l\u2019Universit\u00e9 Laval , 1065 Avenue de la M\u00e9decine, Qu\u00e9bec, Qu\u00e9bec G1V 0A6 ,","place":["Canada"]},{"name":"Institut Intelligence et Donn\u00e9es (IID), Universit\u00e9 Laval , 1065 Avenue de la M\u00e9decine, Qu\u00e9bec, Qu\u00e9bec G1V 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-1040","authenticated-orcid":false,"given":"Yves","family":"Briers","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Ghent University, Valentin Vaerwyckweg 1 , Ghent 9000 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7919-552X","authenticated-orcid":false,"given":"Roberto","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Ghent University, Valentin Vaerwyckweg 1 , Ghent 9000 ,","place":["Belgium"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Av. 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