@article {328707,
	title = {The landscape of tolerated genetic variation in humans and primates.},
	journal = {Science},
	volume = {380},
	year = {2023},
	month = {2023 Jun 02},
	pages = {eabn8153},
	abstract = {<p>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.</p>
},
	keywords = {Animals, Base Sequence, Gene Frequency, Genetic Variation, Humans, Primates, Whole Genome Sequencing},
	issn = {1095-9203},
	doi = {10.1126/science.abn8197},
	url = {https://www.science.org/doi/full/10.1126/science.abn8197?rfr_dat=cr_pub++0pubmed\&url_ver=Z39.88-2003\&rfr_id=ori\%3Arid\%3Acrossref.org},
	author = {Gao, Hong and Hamp, Tobias and Ede, Jeffrey and Schraiber, Joshua G and McRae, Jeremy and Singer-Berk, Moriel and Yang, Yanshen and Dietrich, Anastasia S D and Fiziev, Petko P and Kuderna, Lukas F K and Sundaram, Laksshman and Wu, Yibing and Adhikari, Aashish and Field, Yair and Chen, Chen and Batzoglou, Serafim and Aguet, Francois and Lemire, Gabrielle and Reimers, Rebecca and Balick, Daniel and Janiak, Mareike C and Kuhlwilm, Martin and Orkin, Joseph D and Manu, Shivakumara and Valenzuela, Alejandro and Bergman, Juraj and Rousselle, Marjolaine and Silva, Felipe Ennes and Agueda, Lidia and Blanc, Julie and Gut, Marta and de Vries, Dorien and Goodhead, Ian and Harris, R Alan and Raveendran, Muthuswamy and Jensen, Axel and Chuma, Idriss S and Horvath, Julie E and Hvilsom, Christina and Juan, David and Frandsen, Peter and de Melo, Fabiano R and Bertuol, Fabr{\'\i}cio and Byrne, Hazel and Sampaio, Iracilda and Farias, Izeni and do Amaral, Jo{\~a}o Valsecchi and Messias, Mariluce and da Silva, Maria N F and Trivedi, Mihir and Rossi, Rogerio and Hrbek, Tomas and Andriaholinirina, Nicole and Rabarivola, Cl{\'e}ment J and Zaramody, Alphonse and Jolly, Clifford J and Phillips-Conroy, Jane and Wilkerson, Gregory and Abee, Christian and Simmons, Joe H and Fernandez-Duque, Eduardo and Kanthaswamy, Sree and Shiferaw, Fekadu and Wu, Dongdong and Zhou, Long and Shao, Yong and Zhang, Guojie and Keyyu, Julius D and Knauf, Sascha and Le, Minh D and Lizano, Esther and Merker, Stefan and Navarro, Arcadi and Bataillon, Thomas and Nadler, Tilo and Khor, Chiea Chuen and Lee, Jessica and Tan, Patrick and Lim, Weng Khong and Kitchener, Andrew C and Zinner, Dietmar and Gut, Ivo and Melin, Amanda and Guschanski, Katerina and Schierup, Mikkel Heide and Beck, Robin M D and Umapathy, Govindhaswamy and Roos, Christian and Boubli, Jean P and Lek, Monkol and Sunyaev, Shamil and O{\textquoteright}Donnell-Luria, Anne and Rehm, Heidi L and Xu, Jinbo and Rogers, Jeffrey and Marques-Bonet, Tomas and Farh, Kyle Kai-How}
}
