{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:53:22Z","timestamp":1791564802913,"version":"4.3.4"},"reference-count":0,"publisher":"Cold Spring Harbor Laboratory","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270683"],"award-info":[{"award-number":["32270683"]}],"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":["32470662"],"award-info":[{"award-number":["32470662"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["5242006"],"award-info":[{"award-number":["5242006"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2026ZD0553801"],"award-info":[{"award-number":["2026ZD0553801"]}]},{"name":"the Fundamental Research Funds for the Central Universities","award":["BMU2021YJ064"],"award-info":[{"award-number":["BMU2021YJ064"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genome Res."],"accepted":{"date-parts":[[2026,9,16]]},"abstract":"<jats:p>Cross-species integration of single-cell transcriptomes requires establishing gene correspondences to enable comparative analysis of expression profiles across organisms. Current approaches predominantly rely on Ensembl homology tables; although gene-family expansion and contraction can reflect biologically meaningful evolutionary divergence, default many-to-many mappings can overweight expanded gene-family signals during integration and generate mapping-associated microclusters that lack clear cell-type identity, thereby complicating direct cell-type alignment. Although restricting mappings to a one-to-one scheme suppresses such artifacts, it reduces the number of homology gene pairs by \u223c8% (about 900 pairs). To address this limitation, we develop a protein large language model (pLLM)\u2013based gene homology mapping strategy that boosts the number of homology gene pairs. By enforcing a one-to-one mapping constraint and integrating pLLM-derived representations with sequence similarity, we construct a fused mapping approach, which achieves top performance in a comprehensive benchmark based on a curated cross-species atlas spanning nine data sets, 11 species, and more than 3.2 million cells. Our method further identifies previously unannotated cell-type marker pairs, facilitating novel cross-species marker discovery. These results establish a robust framework for gene homology mapping in cross-species transcriptome integration, improving both accuracy and biological interpretability.<\/jats:p>","DOI":"10.1101\/gr.281566.125","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:10:18Z","timestamp":1791562218000},"source":"Crossref","is-referenced-by-count":0,"title":["Protein large language model\u2013assisted one-to-one gene homology mapping in cross-species single-cell transcriptome integration"],"prefix":"10.1101","author":[{"given":"Ze-Yu","family":"Kuang","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Chen","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Na","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3498-3095","authenticated-orcid":false,"given":"Hua-Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;"},{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China;"},{"name":"Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Center for Precision Medicine Multi-Omics Research, Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2026,10,9]]},"container-title":["Genome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gr.281566.125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:10:19Z","timestamp":1791562219000},"score":1,"resource":{"primary":{"URL":"http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.281566.125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":0,"alternative-id":["10.1101\/gr.281566.125"],"URL":"https:\/\/doi.org\/10.1101\/gr.281566.125","relation":{},"ISSN":["1088-9051","1549-5469"],"issn-type":[{"value":"1088-9051","type":"print"},{"value":"1549-5469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]}}}