Publication Type: Journal Article
Authors: Gao, Hong; Hamp, Tobias; Ede, Jeffrey; Schraiber, Joshua G; McRae, Jeremy; Singer-Berk, Moriel; Yang, Yanshen; Dietrich, Anastasia S D; Fiziev, Petko P; Kuderna, Lukas F K; Sundaram, Laksshman; Wu, Yibing; Adhikari, Aashish; Field, Yair; Chen, Chen; Batzoglou, Serafim; Aguet, Francois; Lemire, Gabrielle; Reimers, Rebecca; Balick, Daniel; Janiak, Mareike C; Kuhlwilm, Martin; Orkin, Joseph D; Manu, Shivakumara; Valenzuela, Alejandro; Bergman, Juraj; Rousselle, Marjolaine; Silva, Felipe Ennes; Agueda, Lidia; Blanc, Julie; Gut, Marta; de Vries, Dorien; Goodhead, Ian; Harris, R Alan; Raveendran, Muthuswamy; Jensen, Axel; Chuma, Idriss S; Horvath, Julie E; Hvilsom, Christina; Juan, David; Frandsen, Peter; de Melo, Fabiano R; Bertuol, Fabrício; Byrne, Hazel; Sampaio, Iracilda; Farias, Izeni; do Amaral, João Valsecchi; Messias, Mariluce; da Silva, Maria N F; Trivedi, Mihir; Rossi, Rogerio; Hrbek, Tomas; Andriaholinirina, Nicole; Rabarivola, Clément J; Zaramody, Alphonse; Jolly, Clifford J; Phillips-Conroy, Jane; Wilkerson, Gregory; Abee, Christian; Simmons, Joe H; Fernandez-Duque, Eduardo; Kanthaswamy, Sree; Shiferaw, Fekadu; Wu, Dongdong; Zhou, Long; Shao, Yong; Zhang, Guojie; Keyyu, Julius D; Knauf, Sascha; Le, Minh D; Lizano, Esther; Merker, Stefan; Navarro, Arcadi; Bataillon, Thomas; Nadler, Tilo; Khor, Chiea Chuen; Lee, Jessica; Tan, Patrick; Lim, Weng Khong; Kitchener, Andrew C; Zinner, Dietmar; Gut, Ivo; Melin, Amanda; Guschanski, Katerina; Schierup, Mikkel Heide; Beck, Robin M D; Umapathy, Govindhaswamy; Roos, Christian; Boubli, Jean P; Lek, Monkol; Sunyaev, Shamil; O'Donnell-Luria, Anne; Rehm, Heidi L; Xu, Jinbo; Rogers, Jeffrey; Marques-Bonet, Tomas; Farh, Kyle Kai-How
Year of Publication: 2023
Journal: Science
Volume: 380
Issue: 6648
Pagination: eabn8153
Date Published: 2023 Jun 02
Publication Language: eng
ISSN: 1095-9203
Keywords: Animals, Base Sequence, Gene Frequency, Genetic Variation, Humans, Primates, Whole Genome Sequencing
Abstract: Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
DOI: 10.1126/science.abn8197
Alternate Journal: Science
