{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:02:21Z","timestamp":1788876141859,"version":"build-2803163510"},"reference-count":29,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemistry and Biophysics Reports"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.bbrep.2025.102049","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T08:28:04Z","timestamp":1747384084000},"page":"102049","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Benchmarking AlphaMissense pathogenicity predictions against APP, PSEN1, and PSEN2 variants of unknown significance"],"prefix":"10.1016","volume":"42","author":[{"given":"Joshua","family":"Pillai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kijung","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengbiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbrep.2025.102049_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2025.102699","article-title":"Hallmarks of aging and Alzheimer's Disease pathogenesis: paving the route for new therapeutic targets","volume":"106","author":"Bellelli","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.bbrep.2025.102049_bib2","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1086\/302553","article-title":"Early-onset autosomal dominant alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum","volume":"65","author":"Campion","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.bbrep.2025.102049_bib3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003685","article-title":"The PSEN1, P.E318G variant increases the risk of Alzheimer's disease in APOE-\u03954 carriers","volume":"9","author":"Benitez","year":"2013","journal-title":"PLoS Genet."},{"key":"10.1016\/j.bbrep.2025.102049_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2020.104817","article-title":"Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2","volume":"139","author":"Hsu","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.bbrep.2025.102049_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.neurot.2025.e00527","article-title":"Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2","author":"Marsh","year":"2025","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.bbrep.2025.102049_bib6","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0297560","article-title":"Benchmarking AlphaMissense pathogenicity predictions against cystic fibrosis variants","volume":"19","author":"McDonald","year":"2024","journal-title":"PLoS One"},{"key":"10.1016\/j.bbrep.2025.102049_bib7","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2024.1487608","article-title":"Comprehensive evaluation of AlphaMissense predictions by evidence quantification for variants of uncertain significance","volume":"15","author":"Kurtovic-Kozaric","year":"2024","journal-title":"Front. Genet."},{"key":"10.1016\/j.bbrep.2025.102049_bib8","doi-asserted-by":"crossref","DOI":"10.1002\/ccr3.8453","article-title":"Predicting valuable missense variants with AlphaMissense in a multiple pulmonary infection patient","volume":"12","author":"Wang","year":"2024","journal-title":"Clin. Case Rep."},{"key":"10.1016\/j.bbrep.2025.102049_bib9","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bbrep.2025.102049_bib10","doi-asserted-by":"crossref","first-page":"W140","DOI":"10.1093\/nar\/gkae413","article-title":"ProtVar: mapping and contextualizing human missense variation","volume":"52","author":"Stephenson","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bbrep.2025.102049_bib11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41586-021-04043-8","article-title":"Disease variant prediction with deep generative models of evolutionary data","volume":"599","author":"Frazer","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.bbrep.2025.102049_bib12","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.bbrep.2025.102049_bib13","doi-asserted-by":"crossref","DOI":"10.1126\/science.adg7492","article-title":"Accurate proteome-wide missense variant effect prediction with AlphaMissense","volume":"381","author":"Cheng","year":"2023","journal-title":"Science"},{"key":"10.1016\/j.bbrep.2025.102049_bib14","volume":"114","author":"Sun","year":"2016"},{"key":"10.1016\/j.bbrep.2025.102049_bib15","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.csbj.2025.01.024","article-title":"Predicting the impact of missense mutations on an unresolved protein's stability, structure, and function: a case study of Alzheimer's disease\u2010associated TREM2 R47H variant","volume":"27","author":"Pillai","year":"2025","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.bbrep.2025.102049_bib16","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.20391","article-title":"Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms","volume":"5","author":"Kober","year":"2016","journal-title":"Elife"},{"key":"10.1016\/j.bbrep.2025.102049_bib17","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1038\/s41380-022-01518-6","article-title":"A\u03b2 profiles generated by Alzheimer's disease causing PSEN1 variants determine the pathogenicity of the mutation and predict age at disease onset","volume":"27","author":"Petit","year":"2022","journal-title":"Mol. Psychiatr."},{"key":"10.1016\/j.bbrep.2025.102049_bib18","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","article-title":"REVEL: an ensemble method for predicting the pathogenicity of rare missense variants","volume":"99","author":"Ioannidis","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.bbrep.2025.102049_bib19","doi-asserted-by":"crossref","first-page":"2881.e1","DOI":"10.1016\/j.neurobiolaging.2014.06.002","article-title":"Investigating the role of rare coding variability in Mendelian dementia genes (APP , PSEN1 , PSEN2 , GRN , MAPT , and PRNP) in late-onset Alzheimer's disease","volume":"35","author":"Sassi","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.bbrep.2025.102049_bib20","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.neurobiolaging.2008.06.012","article-title":"Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP","volume":"31","author":"Guerreiro","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.bbrep.2025.102049_bib21","doi-asserted-by":"crossref","DOI":"10.1002\/0471142905.hg0720s76","article-title":"Predicting functional effect of human missense mutations using PolyPhen\u20102","volume":"76","author":"Adzhubei","year":"2013","journal-title":"Curr. Protocols Human Genetics"},{"key":"10.1016\/j.bbrep.2025.102049_bib22","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bbrep.2025.102049_bib23","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bbrep.2025.102049_bib24","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1038\/s41431-024-01675-y","article-title":"Assessment of ability of AlphaMissense to identify variants affecting susceptibility to common disease","volume":"32","author":"Curtis","year":"2024","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.bbrep.2025.102049_bib25","first-page":"2825","article-title":"SciKit-learn: machine learning in Python","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res."},{"key":"10.1016\/j.bbrep.2025.102049_bib26","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1073\/pnas.1619574114","article-title":"Presenilin-1 mutations and Alzheimer's disease","volume":"114","author":"Kelleher","year":"2017","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.bbrep.2025.102049_bib27","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1073\/pnas.0608332104","article-title":"The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism","volume":"104","author":"Shen","year":"2006","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.bbrep.2025.102049_bib28","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The Amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.bbrep.2025.102049_bib29","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer's disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."}],"container-title":["Biochemistry and Biophysics Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2405580825001360?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2405580825001360?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T11:22:00Z","timestamp":1749036120000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2405580825001360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":29,"alternative-id":["S2405580825001360"],"URL":"https:\/\/doi.org\/10.1016\/j.bbrep.2025.102049","relation":{},"ISSN":["2405-5808"],"issn-type":[{"value":"2405-5808","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Benchmarking AlphaMissense pathogenicity predictions against APP, PSEN1, and PSEN2 variants of unknown significance","name":"articletitle","label":"Article Title"},{"value":"Biochemistry and Biophysics Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbrep.2025.102049","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"102049"}}