{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:07:15Z","timestamp":1772989635492,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Centre for the Mathematical Foundations of Generative AI","award":["P0046811"],"award-info":[{"award-number":["P0046811"]}]},{"DOI":"10.13039\/501100004377","name":"Hong Kong Polytechnic University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004377","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Proteins are essential components of all living organisms and play a critical role in cellular survival. They have a broad range of applications, from clinical treatments to material engineering. This versatility has spurred the development of protein design, with amino acid sequence design being a crucial step in the process. Recent advancements in deep generative models have shown promise for protein sequence design. However, the scarcity of functional protein sequence data for certain types can hinder the training of these models, which often require large datasets. To address this challenge, we propose a hierarchical model named ProteinRG that can generate functional protein sequences using relatively small datasets. ProteinRG begins by generating a representation of a protein sequence, leveraging existing large protein sequence models, before producing a functional protein sequence. We have tested our model on various functional protein sequences and evaluated the results from three perspectives: multiple sequence alignment, t-SNE distribution analysis, and 3D structure prediction. The findings indicate that our generated protein sequences maintain both similarity to the original sequences and consistency with the desired functions. Moreover, our model demonstrates superior performance compared twith other generative models for protein sequence generation.<\/jats:p>","DOI":"10.1093\/bib\/bbag095","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:43:35Z","timestamp":1770813815000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>De novo<\/i>\n                    functional protein sequence generation: overcoming data scarcity through regeneration and large language models"],"prefix":"10.1093","volume":"27","author":[{"given":"Chenyu","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Applied Mathematics , The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3253-654X","authenticated-orcid":false,"given":"Daihai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics , The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-9269","authenticated-orcid":false,"given":"Jian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics , The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong,","place":["China"]},{"name":"Department of Data Science and AI , The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"2026030808003379000_ref1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.sbi.2016.03.006","article-title":"Algorithms for protein design","volume":"39","author":"Gainza","year":"2016","journal-title":"Curr Opin Struct Biol"},{"key":"2026030808003379000_ref2","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/nature19946","article-title":"The coming of age of de novo protein 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