{"id":"W4387770914","doi":"10.1126/science.adf6249","title":"Elucidating the cellular determinants of targeted membrane protein degradation by lysosome-targeting chimeras","year":2023,"lang":"en","type":"article","venue":"Science","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":157,"is_retracted":false,"has_abstract":true,"ca_institutions":"University of British Columbia","funders":"National Institute of General Medical Sciences; National Cancer Institute; National Institutes of Health; National Science Foundation","keywords":"Lysosome; Internalization; Endosome; Cell biology; Asialoglycoprotein receptor; Endocytosis; Biology; Protein targeting; Receptor; Mannose 6-phosphate; Mannose 6-phosphate receptor; Cell surface receptor; Membrane protein; Biochemistry; Membrane; Growth factor","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":[0.0003068796,0.0003352389,0.0002754983,0.0001623034,0.0001547914,0.0006091015,0.0002535339,0.0005403978,0.001188499],"category_scores_gemma":[0.0001973543,0.0001388114,0.0002910549,0.0001174646,0.0004074564,0.0003755392,0.0002639765,0.001074542,0.0003927721],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000858899,"about_ca_system_score_gemma":0.0004007586,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005611596,"about_ca_topic_score_gemma":0.0007384588,"domain_scores_codex":[0.9998304,0.00002915791,0.00002505219,0.00004159423,0.00004495723,0.00002893843],"domain_scores_gemma":[0.9998109,0.00005064514,0.00007105112,0.00002266693,0.00001573405,0.00002905392],"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":[0.00005576812,0.0000133888,0.0001088428,0.00002239209,0.000004538902,0.00003692916,0.00001203023,0.0001660357,0.9985368,0.000425484,0.00001991003,0.0005977227],"study_design_scores_gemma":[0.000005043689,0.00004001449,0.0003959875,0.000002885553,0.00000606434,0.000125428,0.00001379128,0.001314295,0.9964117,0.00004848103,0.001633376,0.000002904163],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9596183,0.001472894,0.03549692,0.0003303915,0.00003902232,0.00008533002,0.00088484,0.0002467343,0.001825588],"genre_scores_gemma":[0.9846539,0.0007388073,0.01204097,0.0000863953,0.000004123131,0.00005819377,0.0005663222,0.00007495323,0.001776332],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001188499,"threshold_uncertainty_score":0.006231785,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.008775173645823664,"score_gpt":0.2477964464566403,"score_spread":0.2390212728108166,"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."}}