{"id":"W4409283259","doi":"10.1016/j.molcel.2025.03.015","title":"MLKL activity requires a splicing-regulated, druggable intramolecular interaction","year":2025,"lang":"en","type":"article","venue":"Molecular Cell","topic":"Melanoma and MAPK Pathways","field":"Biochemistry, Genetics and Molecular Biology","cited_by":9,"is_retracted":false,"has_abstract":true,"ca_institutions":"University of Calgary","funders":"European Research Council; Medical Research Council; Natural Sciences and Engineering Research Council of Canada; Bundesministerium für Bildung und Forschung; Max-Planck-Gesellschaft; Deutsche Forschungsgemeinschaft; Canada Research Chairs; Wellcome Trust; Alexander von Humboldt-Stiftung","keywords":"Biology; Druggability; Intramolecular force; RNA splicing; Alternative splicing; Computational biology; Cell biology; Genetics; Gene; Gene isoform; Stereochemistry; RNA","routes":{"ca_aff":true,"ca_fund":true,"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":[0.000178598,0.0001773701,0.0001318035,0.00005989096,0.00009906295,0.0002239216,0.0001303496,0.0001738176,0.0009696849],"category_scores_gemma":[0.0001694582,0.00007468097,0.0001513705,0.00006180559,0.0002308798,0.0001564055,0.0001787336,0.0004321676,0.0004462552],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001798388,"about_ca_system_score_gemma":0.0001089878,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0000841032,"about_ca_topic_score_gemma":0.0001963187,"domain_scores_codex":[0.9998316,0.00003950028,0.00001745055,0.0000425249,0.00004741652,0.00002159682],"domain_scores_gemma":[0.999828,0.00004020706,0.00006164132,0.00002930439,0.000012076,0.00002877555],"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":[0.00002365133,0.000007306939,0.0001020942,0.000005162259,0.000001364237,0.00003166969,0.00000419203,0.00002522733,0.9991467,0.0001153766,0.000007597297,0.0005296143],"study_design_scores_gemma":[0.000007752213,0.0001041788,0.001028667,0.000001966721,0.000003204113,0.0002614605,0.000006392774,0.000477378,0.9969284,0.00004204682,0.001136701,0.000001886929],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9911029,0.0004084815,0.006991818,0.00007153446,0.00002342426,0.00002564805,0.00007836769,0.00008054757,0.001217304],"genre_scores_gemma":[0.9969921,0.0001106818,0.002035135,0.00003096521,0.000006797912,0.0000104741,0.0001309147,0.00001773398,0.0006652126],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0009696849,"threshold_uncertainty_score":0.003243923,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.00469308000108386,"score_gpt":0.2325744578579075,"score_spread":0.2278813778568237,"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."}}