{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0002598627,0.0004384316,0.0003059711,0.0002194753,0.0002451588,0.0006966348,0.0004407863,0.0006298375,0.002314351],"category_scores_gemma":[0.0003840978,0.0001918075,0.0004660653,0.0001367604,0.0001973229,0.000277939,0.0002178354,0.001057035,0.001052287],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002893553,"about_ca_system_score_gemma":0.0002414456,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0003656644,"about_ca_topic_score_gemma":0.0005033087,"domain_scores_codex":[0.9998779,0.00001547052,0.000008125006,0.00004021723,0.0000351335,0.00002315895],"domain_scores_gemma":[0.999718,0.00008797517,0.00006881773,0.00003054517,0.00003281762,0.00006186763],"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":[0.0008118479,0.00008961006,0.003091162,0.00006352729,0.0000329623,0.002469029,0.00003170419,0.001593859,0.9803821,0.002056992,0.0004573514,0.008919774],"study_design_scores_gemma":[0.000129473,0.0007163273,0.01438127,0.00002698886,0.0001171487,0.004455931,0.00007848286,0.03302584,0.93424,0.002391199,0.01038542,0.0000518836],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9730056,0.0007700664,0.02009597,0.0005023291,0.0001694791,0.00004059898,0.0008670065,0.0003067486,0.004242314],"genre_scores_gemma":[0.9830809,0.000294804,0.01265876,0.000242129,0.00004250981,0.00001037659,0.001217879,0.00005495394,0.002397653],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002314351,"threshold_uncertainty_score":0.007742286,"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."}}