{"id":"W4408244228","doi":"10.1038/s41586-025-08683-y","title":"Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide","year":2025,"lang":"en","type":"article","venue":"Nature","topic":"Receptor Mechanisms and Signaling","field":"Biochemistry, Genetics and Molecular Biology","cited_by":25,"is_retracted":false,"has_abstract":false,"ca_institutions":"University of British Columbia","funders":"Stanford Cardiovascular Institute, School of Medicine, Stanford University; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Stanford Maternal and Child Health Research Institute; Howard Hughes Medical Institute; Stanford Bio-X; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; Stanford Diabetes Research Center; National Institute of General Medical Sciences; American Heart Association","keywords":"Prohormone convertase; Peptide; Prohormone; Melanocortin; Proprotein Convertases; Proglucagon; Leptin; Incretin; Receptor; Glucose homeostasis; Chemistry; Peptide hormone; Glucagon-like peptide-1; Biology; Hormone; Biochemistry; Endocrinology; Insulin; Diabetes mellitus; Obesity","routes":{"ca_aff":true,"ca_fund":false,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0001824011,0.0001262628,0.000119782,0.00004353122,0.0001021921,0.0000260793,0.0001444961,0.001021902,0.00002806214],"category_scores_gemma":[0.00006614893,0.0001162489,0.00008709562,0.0001308543,0.00002156436,0.000003999311,0.00007900787,0.0006266318,0.000007309552],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00002081457,"about_ca_system_score_gemma":0.00006700202,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00001221559,"about_ca_topic_score_gemma":0.000006894127,"domain_scores_codex":[0.9992275,0.00002941527,0.0001265342,0.000311777,0.0001247348,0.0001799862],"domain_scores_gemma":[0.9996088,0.000005689575,0.00004451819,0.0002314374,0.0000669138,0.00004271247],"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":[0.00006175999,0.00003345588,0.005429979,0.00002561126,0.00004582316,0.000002868726,0.00001745145,0.00003352408,0.9519421,0.0002056282,0.04161286,0.0005889522],"study_design_scores_gemma":[0.0004442194,0.000117569,0.008814561,0.00003973054,0.00002425938,0.000003121172,0.00005943447,0.000112275,0.9288886,0.0001597636,0.06121003,0.0001264183],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9871482,0.0009074419,0.003597888,0.0001933927,0.0005288892,0.0002385284,0.00003267565,0.00002766725,0.007325376],"genre_scores_gemma":[0.9954669,0.000153668,0.000791068,0.0007286998,0.0002372594,0.00001106303,0.0001480777,0.00001201547,0.00245126],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.02305347,"threshold_uncertainty_score":0.7881842,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.002333193536394396,"score_gpt":0.2219852714702794,"score_spread":0.219652077933885,"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."}}