{"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":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0001627593,0.0002676386,0.0002148119,0.0001210324,0.0001138618,0.00006159593,0.0002699993,0.0002528501,0.00004028677],"category_scores_gemma":[0.00005189675,0.0002816417,0.0001852609,0.0002217562,0.00006388436,0.000008569425,0.0002139329,0.0001839429,0.00004781221],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00003945188,"about_ca_system_score_gemma":0.0001115932,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00009603338,"about_ca_topic_score_gemma":0.00002016742,"domain_scores_codex":[0.9985144,0.0001209287,0.0002281811,0.0005942624,0.0001586901,0.0003835698],"domain_scores_gemma":[0.9990049,0.00001020821,0.00009788068,0.0007035458,0.00008542685,0.00009806325],"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":[0.0001231905,0.0001309206,0.0001317412,0.00006126129,0.00006616618,0.00004711787,0.00002519477,0.0002363852,0.991217,0.0004037367,0.003326853,0.004230434],"study_design_scores_gemma":[0.0005904636,0.0001682864,0.000180461,0.00003317414,0.00004698714,0.00001003805,0.00003479019,0.0003575454,0.9220979,0.000219424,0.07600696,0.0002539402],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9138655,0.0006619886,0.03173049,0.0002051975,0.0004142787,0.0002951698,0.000006969577,0.00004908593,0.05277133],"genre_scores_gemma":[0.9939572,0.00004875821,0.0006509848,0.0006873154,0.00007868805,0.00004196359,0.00009090782,0.00003536474,0.004408769],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.08009176,"threshold_uncertainty_score":0.9999636,"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."}}