{"id":"W3082311577","doi":"10.7554/elife.58026","title":"Multiplexed measurement of variant abundance and activity reveals VKOR topology, active site and human variant impact","year":2020,"lang":"en","type":"article","venue":"eLife","topic":"Pharmacogenetics and Drug Metabolism","field":"Pharmacology, Toxicology and Pharmaceutics","cited_by":103,"is_retracted":false,"has_abstract":true,"ca_institutions":"Sinai Health System; Lunenfeld-Tanenbaum Research Institute; University of Toronto","funders":"National Institute of General Medical Sciences; National Human Genome Research Institute; Canadian Institutes of Health Research; Canada Excellence Research Chairs, Government of Canada; Chan Zuckerberg Initiative; National Institutes of Health; National Science Foundation","keywords":"Vitamin K epoxide reductase; Biology; Transmembrane domain; Missense mutation; Genetics; Gene; Mutation","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":[0.001111838,0.0002886657,0.0005400758,0.00006663852,0.0002776337,0.00001824753,0.0001688731,0.0002264354,0.0003293174],"category_scores_gemma":[0.000247181,0.0002599306,0.00009455557,0.0001516479,0.0003103385,0.0001106061,0.0001989994,0.0006555742,0.00001270626],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00004347803,"about_ca_system_score_gemma":0.00009410623,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001511215,"about_ca_topic_score_gemma":0.00002357748,"domain_scores_codex":[0.9977936,0.0007107242,0.0003584792,0.0004577419,0.0002690198,0.000410438],"domain_scores_gemma":[0.9986314,0.0002174873,0.0002674286,0.0001690973,0.0001835282,0.0005310941],"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":[0.0007528077,0.0002384113,0.007191593,0.00007765226,0.0003962182,0.00005101057,0.001923071,0.0001020081,0.9806015,0.0004198924,0.0009759481,0.007269894],"study_design_scores_gemma":[0.006535717,0.0005416197,0.2368107,0.00002821466,0.0005858827,0.0000649776,0.0001249446,0.004382691,0.7226058,0.0003191267,0.02740817,0.0005921217],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9945534,0.001874485,0.0002065907,0.001512066,0.0003028709,0.0005124704,0.0003349767,0.00004318526,0.0006599337],"genre_scores_gemma":[0.9966639,0.0007047132,0.0003458368,0.001892868,0.0003011757,0.00002508392,0.000007555961,0.00002493833,0.00003393794],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.2579956,"threshold_uncertainty_score":0.9999853,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.1530283749634961,"score_gpt":0.437107931851903,"score_spread":0.2840795568884069,"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."}}