{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.000126877,0.00007988628,0.0001307586,0.00004205453,0.00001698651,0.000004245089,0.00009346529,0.00006369847,0.000002885785],"category_scores_gemma":[0.00004441242,0.00007911888,0.00003882576,0.00009773166,0.00006756719,0.000001113705,0.0000385332,0.00004257779,1.228663e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00000317089,"about_ca_system_score_gemma":0.00009703276,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00001495288,"about_ca_topic_score_gemma":0.00001559536,"domain_scores_codex":[0.999371,0.00006566889,0.0002111065,0.0001887638,0.00006289718,0.0001005709],"domain_scores_gemma":[0.9996224,0.00002439794,0.00007729108,0.0001975539,0.00005832194,0.0000200403],"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":[0.00008129369,0.00008729266,0.008875255,0.00006398385,0.00002370056,0.00000134445,0.00003539229,0.0001788486,0.9814291,0.0003918489,0.000008698465,0.008823213],"study_design_scores_gemma":[0.00254117,0.0009097931,0.2833231,0.0001057917,0.0001106123,0.000008519535,0.0001376009,0.004009407,0.7026144,0.001649116,0.004261184,0.000329346],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9977058,0.001194456,0.000342668,0.0000441648,0.00005788515,0.000169752,0.000027098,0.000002416899,0.0004557665],"genre_scores_gemma":[0.9987336,0.0003545877,0.0005218881,0.0002596627,0.00001408296,0.000006236061,0.000005406464,0.000008765476,0.00009570689],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.2788148,"threshold_uncertainty_score":0.3226374,"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."}}