{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:57:52Z","timestamp":1791392272265,"version":"4.3.3"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Nucleic-acid-binding proteins (NABPs) govern transcription, replication and genome organization, yet the distribution of aggregation susceptibility within regulatory proteomes remains unresolved. Here, we systematically examine amyloidogenic potential across the nucleic-acid-binding proteomes of four phylogenetically diverse organisms\u2014Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae and Homo sapiens\u2014spanning prokaryotes and eukaryotes, to determine whether aggregation-prone sequence architectures are selectively constrained within transcriptional networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using VAEBAC, a representation-learning framework that integrates large-scale amyloid-family sequences with experimentally validated annotations, we performed proteome-scale prediction of amyloidogenicity across nucleic-acid-binding proteins in each organism. Predicted amyloidogenic proteins were consistently and significantly enriched in Gene Ontology categories associated with regulation of DNA-templated transcription, RNA biosynthesis, and gene expression across all four organisms, a pattern validated using three independent annotation tools. Fisher\u2019s exact test confirmed significant enrichment of amyloidogenic NABPs among transcription regulators in eukaryotic proteomes. Residue-level mapping demonstrated spatial separation between predicted aggregation-prone regions and DNA-binding interfaces, suggesting structural compatibility between regulatory function and conditional aggregation. Experimental validation confirmed fibrillar assembly of selected proteins. These findings support a conserved model in which aggregation susceptibility is functionally stratified across transcriptional regulatory tiers rather than uniformly suppressed within NABPs, a principle conserved across 3.5 billion years of evolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and Implementation<\/jats:title>\n                    <jats:p>VAEBAC is freely accessible at https:\/\/www.vaebac.com.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary Information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag745","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:49:56Z","timestamp":1791373796000},"source":"Crossref","is-referenced-by-count":0,"title":["VAEBAC: A representation-learning framework for proteome-scale prediction of amyloidogenic proteins and functional stratification of nucleic-acid-binding proteins"],"prefix":"10.1093","author":[{"given":"Muhammad Uzair","family":"Ashraf","sequence":"first","affiliation":[{"name":"Aligarh Muslim University Interdisciplinary Biotechnology Unit, Faculty of Life Sciences, , 202002, Uttar Pradesh,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owais","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Aligarh Muslim University Interdisciplinary Biotechnology Unit, Faculty of Life Sciences, , 202002, Uttar Pradesh,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwan Hasan","family":"Khan","sequence":"additional","affiliation":[{"name":"Aligarh Muslim University Interdisciplinary Biotechnology Unit, Faculty of Life Sciences, , 202002, Uttar Pradesh,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,7]]},"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btag745\/71666842\/btag745.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btag745\/71666842\/btag745.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:35:07Z","timestamp":1791390907000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article\/doi\/10.1093\/bioinformatics\/btag745\/8875881"}},"subtitle":[],"editor":[{"given":"Daisuke","family":"Kihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btag745","relation":{},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"btag745"}}