{"id":"W3029661147","doi":"10.1038/s41586-020-2308-7","title":"The mutational constraint spectrum quantified from variation in 141,456 humans","year":2020,"lang":"en","type":"article","venue":"Nature","topic":"Genomics and Rare Diseases","field":"Biochemistry, Genetics and Molecular Biology","cited_by":10127,"is_retracted":false,"has_abstract":true,"ca_institutions":"Université de Montréal; Montreal Heart Institute; University of Ottawa","funders":"Common Fund; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences; National Institute on Aging; Sanofi Genzyme; National Institute of Mental Health; National Heart, Lung, and Blood Institute; National Institutes of Health; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; National Cancer Institute; British Heart Foundation; National Center for Advancing Translational Sciences; National Human Genome Research Institute; Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Sanofi; Rosetrees Trust; BioMarin Pharmaceutical; National Science Foundation","keywords":"Gene; Genome; Biology; Computational biology; Annotation; Exome sequencing; Human genome; Genetics; Exome; Loss function; Phenotype; Function (biology); Mutation","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":[0.000788631,0.0002394352,0.0004111938,0.001543389,0.0004118122,0.0005879323,0.0002418387,0.0003279361,0.001426102],"category_scores_gemma":[0.002796918,0.0001290797,0.0003275965,0.001828363,0.0002861559,0.0001819048,0.0005011628,0.0001716355,0.0002226882],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002206171,"about_ca_system_score_gemma":0.0001422098,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.002915419,"about_ca_topic_score_gemma":0.002927333,"domain_scores_codex":[0.9992219,0.0001876964,0.00006624941,0.0003516831,0.0001229372,0.00004953861],"domain_scores_gemma":[0.9988906,0.0006101606,0.0001963602,0.000154857,0.00008238634,0.00006564229],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"observational","study_design_gemma":"observational","study_design_scores_codex":[0.0005724869,0.00003912507,0.9509937,0.00007798748,0.0003884568,0.0005785206,0.0004028555,0.006159015,0.01726541,0.001029234,0.0007052557,0.02178789],"study_design_scores_gemma":[0.00001833418,0.00007806854,0.9842098,0.00001111742,0.00008117905,0.001026544,0.0001386796,0.00929849,0.001738491,0.001548025,0.001833159,0.00001811882],"study_design_candidate":"observational","study_design_consensus":"observational","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9970694,0.0001234821,0.001158292,0.00001363225,0.000001329939,0.000004686936,0.00128579,0.00001580463,0.0003276221],"genre_scores_gemma":[0.9958264,0.00007472875,0.0009420927,0.00001368416,0.000003824559,0.00001093694,0.003008833,0.000009937119,0.0001094324],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002915419,"threshold_uncertainty_score":0.005796969,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.007021155401284386,"score_gpt":0.2355262804310669,"score_spread":0.2285051250297825,"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."}}