{"id":"W4406872799","doi":"10.1016/j.neurot.2025.e00527","title":"Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2","year":2025,"lang":"en","type":"article","venue":"Neurotherapeutics","topic":"Genomics and Rare Diseases","field":"Biochemistry, Genetics and Molecular Biology","cited_by":7,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Instituto de Salud Carlos III; Canadian Institutes of Health Research; Deutsches Zentrum für Neurodegenerative Erkrankungen; Fonds de Recherche du Québec - Santé; Fondation Brain Canada; Ministry of Science and ICT, South Korea; Ministry of Health and Welfare; Korea Health Industry Development Institute; Korea Dementia Research Center; Japan Agency for Medical Research and Development; Fleni; National Institute on Aging; Alzheimer's Association","keywords":"Pathogenicity; PSEN1; Neurology; Biology; Genetics; Computational biology; Neuroscience; Medicine; Pathology; Disease; Alzheimer's disease; Presenilin; Microbiology","routes":{"ca_aff":false,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":true},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.001066411,0.0004786398,0.0004368446,0.0009915215,0.0003304632,0.0006510681,0.0002420008,0.0005498892,0.0008667595],"category_scores_gemma":[0.002232475,0.000102585,0.0003527499,0.0006179673,0.0003533584,0.0002364589,0.0003116086,0.0004299585,0.0002321074],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002319495,"about_ca_system_score_gemma":0.0002155331,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005734554,"about_ca_topic_score_gemma":0.001250297,"domain_scores_codex":[0.9993809,0.0001516283,0.00008592095,0.0001399334,0.0001954682,0.00004604064],"domain_scores_gemma":[0.9986801,0.000808441,0.0002498763,0.00007756002,0.00010802,0.00007607938],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.002183126,0.0002081699,0.3710797,0.0004403804,0.0005259376,0.006718948,0.0004025589,0.002489107,0.564768,0.0008933494,0.0005826855,0.04970806],"study_design_scores_gemma":[0.0001564563,0.001638943,0.609607,0.0001603839,0.0009323152,0.03147137,0.0005059178,0.01885367,0.3252375,0.002963078,0.008375116,0.00009815918],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9936312,0.001953225,0.00307204,0.00008390913,0.00002430369,0.0000273801,0.0004759662,0.00004491782,0.0006870577],"genre_scores_gemma":[0.9959741,0.0004793519,0.002801107,0.00005777827,0.00001311617,0.000009691697,0.0004684313,0.00001049525,0.000185936],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001066411,"threshold_uncertainty_score":0.005639791,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02336464684340202,"score_gpt":0.3285196340895656,"score_spread":0.3051549872461636,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}