{"doi":"10.1038/s41586-020-2329-2","title":"Transcript expression-aware annotation improves rare variant interpretation","abstract":"The acceleration of DNA sequencing in samples from patients and population studies has resulted in extensive catalogues of human genetic variation, but the interpretation of rare genetic variants remains problematic. A notable example of this challenge is the existence of disruptive variants in dosage-sensitive disease genes, even in apparently healthy individuals. Here, by manual curation of putative loss-of-function (pLoF) variants in haploinsufficient disease genes in the Genome Aggregation Database (gnomAD)<sup>1</sup>, we show that one explanation for this paradox involves alternative splicing of mRNA, which allows exons of a gene to be expressed at varying levels across different cell types. Currently, no existing annotation tool systematically incorporates information about exon expression into the interpretation of variants. We develop a transcript-level annotation metric known as the 'proportion expressed across transcripts', which quantifies isoform expression for variants. We calculate this metric using 11,706 tissue samples from the Genotype Tissue Expression (GTEx) project<sup>2</sup> and show that it can differentiate between weakly and highly evolutionarily conserved exons, a proxy for functional importance. We demonstrate that expression-based annotation selectively filters 22.8% of falsely annotated pLoF variants found in haploinsufficient disease genes in gnomAD, while removing less than 4% of high-confidence pathogenic variants in the same genes. Finally, we apply our expression filter to the analysis of de novo variants in patients with autism spectrum disorder and intellectual disability or developmental disorders to show that pLoF variants in weakly expressed regions have similar effect sizes to those of synonymous variants, whereas pLoF variants in highly expressed exons are most strongly enriched among cases. Our annotation is fast, flexible and generalizable, making it possible for any variant file to be annotated with any isoform expression dataset, and will be valuable for the genetic diagnosis of rare diseases, the analysis of rare variant burden in complex disorders, and the curation and prioritization of variants in recall-by-genotype studies.","journal":"Nature","year":2020,"id":9857,"datarank":0.7962401546101808,"base_score":5.308267697401205,"endowment":5.308267697401205,"self_citation_contribution":0.7962401546101808,"citation_network_contribution":0.0,"self_endowment_contribution":0.7962401546101808,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":201,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0877,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-05-27","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":47,"name":"Konrad J. Karczewski","orcid":"0000-0003-2878-4671","position":1,"is_corresponding":false},{"id":62343,"name":"Ditte Demontis","orcid":"0000-0001-9124-2766","position":2,"is_corresponding":false},{"id":981,"name":"Eleanor G. Seaby","orcid":"0000-0002-6814-8648","position":3,"is_corresponding":false},{"id":977,"name":"Nicholas A. Watts","orcid":null,"position":4,"is_corresponding":false},{"id":979,"name":"Moriel Singer-Berk","orcid":null,"position":5,"is_corresponding":false},{"id":24517,"name":"Shinichi Morishita","orcid":"0000-0002-6201-8885","position":6,"is_corresponding":false},{"id":5256,"name":"Christel M. Middeldorp","orcid":"0000-0002-6218-0428","position":7,"is_corresponding":false},{"id":19865,"name":"F. Kyle Satterstrom","orcid":"0000-0001-6187-7680","position":8,"is_corresponding":false},{"id":995,"name":"Anne H. O’Donnell-Luria","orcid":"0000-0001-6418-9592","position":9,"is_corresponding":false},{"id":987,"name":"Timothy Poterba","orcid":"0000-0003-1287-3434","position":10,"is_corresponding":false},{"id":989,"name":"Cotton Seed","orcid":null,"position":11,"is_corresponding":false},{"id":976,"name":"Matthew Solomonson","orcid":"0000-0002-5344-9026","position":12,"is_corresponding":false},{"id":968,"name":"Jessica Alföldi","orcid":"0000-0001-9713-6200","position":13,"is_corresponding":false},{"id":1001,"name":"Irina M. Armean","orcid":"0000-0002-1043-4756","position":16,"is_corresponding":false},{"id":62020,"name":"Iain Mathieson","orcid":"0000-0002-4256-3982","position":17,"is_corresponding":false},{"id":1002,"name":"Louis Bergelson","orcid":null,"position":18,"is_corresponding":false},{"id":1003,"name":"Kristian Cibulskis","orcid":"0000-0003-1343-1582","position":19,"is_corresponding":false},{"id":970,"name":"Ryan L. Collins","orcid":"0000-0003-1268-9995","position":20,"is_corresponding":false},{"id":1004,"name":"Kristen M. Connolly","orcid":null,"position":21,"is_corresponding":false},{"id":1005,"name":"Miguel Covarrubias","orcid":null,"position":22,"is_corresponding":false},{"id":24722,"name":"Coleen Damcott","orcid":"0000-0001-6233-7395","position":24,"is_corresponding":false},{"id":1006,"name":"Stacey Donnelly","orcid":"0000-0001-5732-3300","position":25,"is_corresponding":false},{"id":985,"name":"Yossi Farjoun","orcid":"0000-0002-7002-2868","position":26,"is_corresponding":false},{"id":1007,"name":"Steven Ferriera","orcid":null,"position":27,"is_corresponding":false},{"id":27305,"name":"Anthony Philippakis","orcid":"0000-0001-6953-3794","position":28,"is_corresponding":false},{"id":974,"name":"Laura D. Gauthier","orcid":null,"position":30,"is_corresponding":false},{"id":1009,"name":"Jeff Gentry","orcid":null,"position":31,"is_corresponding":false},{"id":1010,"name":"Namrata Gupta","orcid":"0000-0001-6786-4995","position":32,"is_corresponding":false},{"id":1011,"name":"Thibault Jeandet","orcid":null,"position":33,"is_corresponding":false},{"id":1012,"name":"Diane Kaplan","orcid":null,"position":34,"is_corresponding":false},{"id":971,"name":"Kristen M. Laricchia","orcid":"0000-0002-0733-8341","position":36,"is_corresponding":false},{"id":1013,"name":"Christopher Llanwarne","orcid":null,"position":37,"is_corresponding":false},{"id":5010,"name":"Eric V. Minikel","orcid":null,"position":38,"is_corresponding":false},{"id":1015,"name":"Sam Novod","orcid":null,"position":41,"is_corresponding":false},{"id":1016,"name":"Nikelle Petrillo","orcid":null,"position":43,"is_corresponding":false},{"id":1017,"name":"David Roazen","orcid":null,"position":45,"is_corresponding":false},{"id":14828,"name":"Manuel A. Rivas","orcid":"0000-0003-1457-9925","position":46,"is_corresponding":false},{"id":1019,"name":"Andrea Saltzman","orcid":"0000-0002-0335-9196","position":47,"is_corresponding":false},{"id":992,"name":"Kaitlin E. Samocha","orcid":"0000-0002-1704-3352","position":48,"is_corresponding":false},{"id":1020,"name":"Molly Schleicher","orcid":null,"position":49,"is_corresponding":false},{"id":1021,"name":"Jose Soto","orcid":null,"position":52,"is_corresponding":false},{"id":966,"name":"Grace Tiao","orcid":"0000-0001-9864-8275","position":53,"is_corresponding":false},{"id":1022,"name":"Kathleen Tibbetts","orcid":null,"position":54,"is_corresponding":false},{"id":1023,"name":"Charlotte Tolonen","orcid":null,"position":55,"is_corresponding":false},{"id":1000,"name":"Christopher Vittal","orcid":null,"position":56,"is_corresponding":false},{"id":1024,"name":"Gordon Wade","orcid":null,"position":57,"is_corresponding":false},{"id":988,"name":"Arcturus Wang","orcid":null,"position":58,"is_corresponding":false},{"id":997,"name":"Ben Weisburd","orcid":"0000-0001-9898-9109","position":62,"is_corresponding":false},{"id":990,"name":"Nicola Whiffin","orcid":"0000-0003-1554-6594","position":63,"is_corresponding":false},{"id":1026,"name":"Genome Aggregation Database Consortium","orcid":null,"position":64,"is_corresponding":false},{"id":1027,"name":"Carlos A. Aguilar Salinas","orcid":null,"position":65,"is_corresponding":false},{"id":5021,"name":"Carlos A. Aguilar-Salinas","orcid":null,"position":66,"is_corresponding":false},{"id":1029,"name":"Christine M. Albert","orcid":"0000-0002-2081-1121","position":67,"is_corresponding":false},{"id":1030,"name":"Diego Ardissino","orcid":"0000-0003-0410-3528","position":68,"is_corresponding":false},{"id":1031,"name":"Gil Atzmon","orcid":"0000-0001-6895-3607","position":69,"is_corresponding":false},{"id":1032,"name":"John Barnard","orcid":"0000-0003-2403-8268","position":70,"is_corresponding":false},{"id":1034,"name":"Emelia J. Benjamin","orcid":"0000-0003-4076-2336","position":72,"is_corresponding":false},{"id":1035,"name":"Michael Boehnke","orcid":"0000-0002-6442-7754","position":73,"is_corresponding":false},{"id":7147,"name":"Themistocles L. Assimes","orcid":"0000-0003-2349-0009","position":74,"is_corresponding":false},{"id":1037,"name":"Erwin P. Bottinger","orcid":null,"position":75,"is_corresponding":false},{"id":1038,"name":"Donald W. Bowden","orcid":"0000-0003-4861-8005","position":76,"is_corresponding":false},{"id":1039,"name":"Matthew J. Bown","orcid":"0000-0002-6180-3611","position":77,"is_corresponding":false},{"id":24714,"name":"Lee-Ming Chuang","orcid":null,"position":81,"is_corresponding":false},{"id":1044,"name":"Mina K. Chung","orcid":"0000-0002-7835-6045","position":82,"is_corresponding":false},{"id":1045,"name":"Bruce Cohen","orcid":null,"position":83,"is_corresponding":false},{"id":1046,"name":"Adolfo Correa","orcid":"0000-0002-9501-600X","position":84,"is_corresponding":false},{"id":5363,"name":"Anders D. Børglum","orcid":"0000-0001-8627-7219","position":85,"is_corresponding":false},{"id":1049,"name":"Dawood Darbar","orcid":"0000-0002-4103-5977","position":87,"is_corresponding":false},{"id":1050,"name":"Ravindranath Duggirala","orcid":"0000-0003-4761-597X","position":88,"is_corresponding":false},{"id":1051,"name":"Josée Dupuis","orcid":"0000-0003-2871-3603","position":89,"is_corresponding":false},{"id":896,"name":"Patrick T. Ellinor","orcid":"0000-0002-2067-0533","position":90,"is_corresponding":false},{"id":21866,"name":"John Danesh","orcid":"0000-0003-1158-6791","position":91,"is_corresponding":false},{"id":5328,"name":"Katharina Domschke","orcid":"0000-0002-2550-9132","position":92,"is_corresponding":false},{"id":1054,"name":"Tõnu Esko","orcid":null,"position":93,"is_corresponding":false},{"id":1055,"name":"Martti Färkkilä","orcid":null,"position":94,"is_corresponding":false},{"id":95063,"name":"Simon J. Foote","orcid":"0000-0002-9142-2107","position":95,"is_corresponding":false},{"id":29295,"name":"Ellen Todres","orcid":"0000-0001-9289-4432","position":96,"is_corresponding":false},{"id":1058,"name":"Gad Getz","orcid":"0000-0002-0936-0753","position":97,"is_corresponding":false},{"id":1059,"name":"Benjamin Glaser","orcid":null,"position":98,"is_corresponding":false},{"id":1060,"name":"Stephen J. Glatt","orcid":"0000-0002-0360-7567","position":99,"is_corresponding":false},{"id":1061,"name":"David Goldstein","orcid":null,"position":100,"is_corresponding":false},{"id":1062,"name":"Clicerio Gonzalez","orcid":null,"position":101,"is_corresponding":false},{"id":1063,"name":"Leif Groop","orcid":"0000-0002-0187-3263","position":102,"is_corresponding":false},{"id":1064,"name":"Craig Hanis","orcid":null,"position":104,"is_corresponding":false},{"id":1065,"name":"Matthew Harms","orcid":"0000-0002-3395-1633","position":105,"is_corresponding":false},{"id":1066,"name":"Mikko Hiltunen","orcid":"0000-0003-3566-4096","position":106,"is_corresponding":false},{"id":208,"name":"Catherine H. Wilson","orcid":"0000-0002-5333-0295","position":107,"is_corresponding":false},{"id":1068,"name":"Christina M. Hultman","orcid":"0000-0002-0327-2410","position":108,"is_corresponding":false},{"id":21895,"name":"Kevin B. Jacobs","orcid":"0000-0002-4657-6473","position":109,"is_corresponding":false},{"id":1070,"name":"Jaakko Kaprio","orcid":"0000-0002-3716-2455","position":110,"is_corresponding":false},{"id":1071,"name":"Sekar Kathiresan","orcid":"0000-0002-6724-032X","position":111,"is_corresponding":false},{"id":1072,"name":"Bong-Jo Kim","orcid":null,"position":112,"is_corresponding":false},{"id":5333,"name":"Kenneth S. Kendler","orcid":"0000-0001-8689-6570","position":113,"is_corresponding":false},{"id":21900,"name":"Manfred Kayser","orcid":"0000-0002-4958-847X","position":114,"is_corresponding":false},{"id":21902,"name":"Sirkka M Keinanen-Kiukaanniemi","orcid":null,"position":115,"is_corresponding":false},{"id":1076,"name":"Seppo Koskinen","orcid":"0000-0003-1572-1735","position":116,"is_corresponding":false},{"id":1077,"name":"Harlan M. Krumholz","orcid":"0000-0003-2046-127X","position":117,"is_corresponding":false},{"id":1078,"name":"Subra Kugathasan","orcid":"0000-0002-8686-4189","position":118,"is_corresponding":false},{"id":21963,"name":"J. Wouter Jukema","orcid":"0000-0002-3246-8359","position":119,"is_corresponding":false},{"id":21907,"name":"Johanna Kuusisto","orcid":"0000-0001-6550-3176","position":120,"is_corresponding":false},{"id":1081,"name":"Terho Lehtimäki","orcid":"0000-0002-2555-4427","position":121,"is_corresponding":false},{"id":1082,"name":"Ruth J. F. Loos","orcid":"0000-0002-8532-5087","position":122,"is_corresponding":false},{"id":1083,"name":"Steven A. Lubitz","orcid":"0000-0002-9599-4866","position":123,"is_corresponding":false},{"id":52736,"name":"Stuart A. Cook","orcid":"0000-0001-6628-194X","position":124,"is_corresponding":false},{"id":1085,"name":"Daniel G. MacArthur","orcid":"0000-0002-5771-2290","position":125,"is_corresponding":false},{"id":1086,"name":"Jaume Marrugat","orcid":"0000-0003-3320-554X","position":126,"is_corresponding":false},{"id":21998,"name":"Jacques S Beckmann","orcid":null,"position":128,"is_corresponding":false},{"id":1089,"name":"Mark I. McCarthy","orcid":"0000-0002-4393-0510","position":129,"is_corresponding":false},{"id":1090,"name":"Dermot McGovern","orcid":"0000-0001-5621-759X","position":130,"is_corresponding":false},{"id":1091,"name":"Ruth McPherson","orcid":"0000-0002-9087-6107","position":131,"is_corresponding":false},{"id":1092,"name":"James B. Meigs","orcid":"0000-0002-2439-2657","position":132,"is_corresponding":false},{"id":14700,"name":"Matthew B. McQueen","orcid":"0000-0002-7035-6112","position":133,"is_corresponding":false},{"id":1097,"name":"Michael C. O’Donovan","orcid":null,"position":137,"is_corresponding":false},{"id":1098,"name":"Dost Ongur","orcid":null,"position":138,"is_corresponding":false},{"id":1099,"name":"Lorena Orozco","orcid":"0000-0002-5801-9180","position":139,"is_corresponding":false},{"id":1100,"name":"Michael J. Owen","orcid":"0000-0003-4798-0862","position":140,"is_corresponding":false},{"id":1102,"name":"Aarno Palotie","orcid":"0000-0002-2527-5874","position":142,"is_corresponding":false},{"id":1103,"name":"Kyong Soo Park","orcid":"0000-0003-3597-342X","position":143,"is_corresponding":false},{"id":1104,"name":"Carlos Pato","orcid":null,"position":144,"is_corresponding":false},{"id":1105,"name":"Ann E. Pulver","orcid":"0000-0002-5929-9161","position":145,"is_corresponding":false},{"id":1106,"name":"Nazneen Rahman","orcid":"0000-0003-4376-0440","position":146,"is_corresponding":false},{"id":95112,"name":"Richard Reynolds","orcid":"0000-0003-4622-4694","position":147,"is_corresponding":false},{"id":1108,"name":"John D. Rioux","orcid":"0000-0001-7560-8326","position":148,"is_corresponding":false},{"id":1109,"name":"Samuli Ripatti","orcid":"0000-0002-0504-1202","position":149,"is_corresponding":false},{"id":1110,"name":"Dan M. Roden","orcid":"0000-0002-6302-0389","position":150,"is_corresponding":false},{"id":3816,"name":"Douglas M. Ruderfer","orcid":"0000-0002-2365-386X","position":151,"is_corresponding":false},{"id":1112,"name":"Veikko Salomaa","orcid":"0000-0001-7563-5324","position":152,"is_corresponding":false},{"id":1113,"name":"Nilesh J. Samani","orcid":"0000-0002-3286-8133","position":153,"is_corresponding":false},{"id":21821,"name":"Serena Sanna","orcid":"0000-0002-3768-1749","position":154,"is_corresponding":false},{"id":1115,"name":"Heribert Schunkert","orcid":"0000-0001-6428-3001","position":155,"is_corresponding":false},{"id":1118,"name":"Hilkka Soininen","orcid":"0000-0002-2785-9937","position":158,"is_corresponding":false},{"id":1119,"name":"Harry Sokol","orcid":"0000-0002-2914-1822","position":159,"is_corresponding":false},{"id":213,"name":"Patrick F. Sullivan","orcid":"0000-0002-6619-873X","position":161,"is_corresponding":false},{"id":1121,"name":"Jaana Suvisaari","orcid":"0000-0001-7167-0990","position":162,"is_corresponding":false},{"id":1122,"name":"E. Shyong Tai","orcid":"0000-0003-2929-8966","position":163,"is_corresponding":false},{"id":21983,"name":"Harold Snieder","orcid":"0000-0003-1949-2298","position":164,"is_corresponding":false},{"id":1124,"name":"Tuomi Tiinamaija","orcid":null,"position":165,"is_corresponding":false},{"id":1125,"name":"Ming Tsuang","orcid":null,"position":166,"is_corresponding":false},{"id":1126,"name":"Dan Turner","orcid":"0000-0002-3704-3325","position":167,"is_corresponding":false},{"id":1127,"name":"Teresa Tusie-Luna","orcid":null,"position":168,"is_corresponding":false},{"id":1128,"name":"Erkki Vartiainen","orcid":"0000-0001-7498-4389","position":169,"is_corresponding":false},{"id":1129,"name":"Marquis P. Vawter","orcid":"0000-0002-7987-6309","position":170,"is_corresponding":false},{"id":1130,"name":"Hugh Watkins","orcid":"0000-0002-5287-9016","position":172,"is_corresponding":false},{"id":1131,"name":"Rinse K. Weersma","orcid":"0000-0001-7928-7371","position":173,"is_corresponding":false},{"id":63161,"name":"Hugh C. Watkins","orcid":null,"position":174,"is_corresponding":false},{"id":1133,"name":"James G. Wilson","orcid":"0009-0002-0283-2970","position":175,"is_corresponding":false},{"id":5342,"name":"Preben Bo Mortensen","orcid":"0000-0002-5230-9865","position":176,"is_corresponding":false},{"id":1136,"name":"Moriel Singer‐Berk","orcid":"0000-0001-8148-0648","position":179,"is_corresponding":false},{"id":965,"name":"Laurent C. Francioli","orcid":"0000-0002-3039-8895","position":180,"is_corresponding":false},{"id":996,"name":"Eric Vallabh Minikel","orcid":"0000-0003-2206-1608","position":181,"is_corresponding":false},{"id":1139,"name":"Valentín Ruano-Rubio","orcid":null,"position":182,"is_corresponding":false},{"id":1140,"name":"José Soto","orcid":"0000-0002-0317-6664","position":183,"is_corresponding":false},{"id":969,"name":"Qingbo S. Wang","orcid":"0000-0002-9110-5830","position":184,"is_corresponding":false},{"id":1141,"name":"Carlos A. Aguilar‐Salinas","orcid":"0000-0001-8517-0241","position":185,"is_corresponding":false},{"id":1142,"name":"Erwin P. Böttinger","orcid":"0000-0001-6868-6676","position":186,"is_corresponding":false},{"id":1143,"name":"Juliana C.N. Chan","orcid":"0000-0003-1325-1194","position":187,"is_corresponding":false},{"id":16114,"name":"Timothy M. Frayling","orcid":"0000-0001-8362-2603","position":188,"is_corresponding":false},{"id":18447,"name":"Sameer Chavan","orcid":"0000-0002-0220-0845","position":189,"is_corresponding":false},{"id":1146,"name":"Bruce M. Cohen","orcid":null,"position":190,"is_corresponding":false},{"id":1147,"name":"Roberto Elosúa","orcid":"0000-0001-8235-0095","position":191,"is_corresponding":false},{"id":1148,"name":"Tōnu Esko","orcid":"0000-0003-1982-6569","position":192,"is_corresponding":false},{"id":1149,"name":"Martti Färkkilâ","orcid":"0000-0002-0250-8559","position":193,"is_corresponding":false},{"id":1150,"name":"José C. Florez","orcid":"0000-0002-1730-9325","position":194,"is_corresponding":false},{"id":1151,"name":"André Franke","orcid":"0000-0003-1530-5811","position":195,"is_corresponding":false},{"id":1152,"name":"Benjamin Gläser","orcid":"0000-0003-4711-5000","position":196,"is_corresponding":false},{"id":1153,"name":"Clicerio González","orcid":"0000-0003-2419-1086","position":197,"is_corresponding":false},{"id":22054,"name":"Per‐Henrik Groop","orcid":"0000-0003-4055-6954","position":198,"is_corresponding":false},{"id":731,"name":"Bogdan Paşaniuc","orcid":"0000-0002-0227-2056","position":199,"is_corresponding":false},{"id":1155,"name":"Matti Holi","orcid":"0000-0003-3568-7407","position":200,"is_corresponding":false},{"id":1156,"name":"Jaspal S. Kooner","orcid":"0000-0003-2086-4837","position":201,"is_corresponding":false},{"id":1157,"name":"Ronald C.W.","orcid":"0000-0002-1227-803X","position":202,"is_corresponding":false},{"id":1158,"name":"Steven A. McCarroll","orcid":"0000-0002-6954-8184","position":203,"is_corresponding":false},{"id":1159,"name":"Michael C O'Donovan","orcid":"0000-0001-7073-2379","position":204,"is_corresponding":false},{"id":1160,"name":"Döst Öngür","orcid":"0000-0001-8151-5759","position":205,"is_corresponding":false},{"id":1161,"name":"Carlos N. Pato","orcid":"0000-0002-5858-266X","position":206,"is_corresponding":false},{"id":1162,"name":"Jeremiah M. Scharf","orcid":"0000-0002-4742-5896","position":207,"is_corresponding":false},{"id":1163,"name":"M. Benjamin Shoemaker","orcid":"0000-0001-6824-7155","position":208,"is_corresponding":false},{"id":21985,"name":"Matti Uusitupa","orcid":"0000-0001-6052-2001","position":209,"is_corresponding":false},{"id":1165,"name":"Jaakko Tuomilehto","orcid":"0000-0002-8306-6202","position":210,"is_corresponding":false},{"id":21986,"name":"Pim van der Harst","orcid":"0000-0002-2713-686X","position":211,"is_corresponding":false},{"id":1167,"name":"Teresa Tusié‐Luna","orcid":null,"position":212,"is_corresponding":false},{"id":967,"name":"Beryl B. Cummings","orcid":"0000-0001-6346-1646","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}