{"id":"W3196944163","doi":"10.1101/2021.09.07.459271","title":"Can two wrongs make a right? F508del-CFTR ion channel rescue by second-site mutations in its transmembrane domains","year":2021,"lang":"en","type":"preprint","venue":"bioRxiv (Cold Spring Harbor Laboratory)","topic":"Cystic Fibrosis Research Advances","field":"Medicine","cited_by":0,"is_retracted":false,"has_abstract":true,"ca_institutions":"University of Calgary","funders":"Canadian Institutes of Health Research; University College Cork; Canada Research Chairs; University College London; University of Cambridge; Cystic Fibrosis Trust; Compute Canada","keywords":"Cystic fibrosis transmembrane conductance regulator; Transmembrane domain; Chemistry; Hydrogen bond; Potentiator; Transmembrane protein; ATP-binding cassette transporter; Biophysics; Mutagenesis; Cyclic nucleotide-binding domain; Mutation; Crystallography; Stereochemistry; Biochemistry; Peptide sequence; Membrane; Biology; Genetics; Molecule; Transporter","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":[0.0006034566,0.0003095421,0.0005619362,0.0001821341,0.0006300429,0.0005348988,0.0004845522,0.001551365,0.002050655],"category_scores_gemma":[0.001330914,0.000173767,0.0004996327,0.0001108547,0.0009279316,0.001063969,0.0007054012,0.001445324,0.0005918102],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000325822,"about_ca_system_score_gemma":0.0004862435,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001007275,"about_ca_topic_score_gemma":0.001288622,"domain_scores_codex":[0.9997657,0.00004354617,0.00001611708,0.000044238,0.00007577918,0.00005463617],"domain_scores_gemma":[0.9995516,0.0001353566,0.00008634934,0.00007694269,0.00004680784,0.0001028573],"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":[0.002906152,0.0005892173,0.01360093,0.0004036061,0.0004249047,0.01074416,0.001342931,0.01639011,0.8804656,0.0272488,0.01004778,0.0358358],"study_design_scores_gemma":[0.001083818,0.003183018,0.02930154,0.0007687933,0.0006298401,0.02318333,0.005721842,0.1123555,0.6156682,0.08128724,0.1261449,0.000671997],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9805508,0.001513402,0.00688561,0.005223657,0.0007300957,0.00002938845,0.0001739536,0.0002862108,0.004606857],"genre_scores_gemma":[0.994455,0.0003450641,0.002427286,0.0008313924,0.00002563618,0.00001126671,0.00007831088,0.00006979017,0.00175614],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002050655,"threshold_uncertainty_score":0.006860197,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01218742755404391,"score_gpt":0.2580361086865148,"score_spread":0.2458486811324709,"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."}}