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The landscape of tolerated genetic variation in humans and primates. / 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.
In:
Science (New York, N.Y.), Vol. 380, No. 6648, 2023.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Gao, H, Hamp, T, Ede, J, Schraiber, JG, McRae, J, Singer-Berk, M, Yang, Y, Dietrich, ASD, Fiziev, PP, Kuderna, LFK, Sundaram, L, Wu, Y, Adhikari, A, Field, Y, Chen, C, Batzoglou, S, Aguet, F, Lemire, G, Reimers, R, Balick, D, Janiak, MC, Kuhlwilm, M, Orkin, JD, Manu, S, Valenzuela, A, Bergman, J, Rousselle, M, Silva, FE, Agueda, L, Blanc, J, Gut, M, de Vries, D, Goodhead, I, Harris, RA, Raveendran, M, Jensen, A, Chuma, IS, Horvath, JE, Hvilsom, C, Juan, D, Frandsen, P, de Melo, FR, Bertuol, F, Byrne, H, Sampaio, I, Farias, I, do Amaral, JV, Messias, M, da Silva, MNF, Trivedi, M, Rossi, R, Hrbek, T, Andriaholinirina, N, Rabarivola, CJ, Zaramody, A, Jolly, CJ, Phillips-Conroy, J, Wilkerson, G, Abee, C, Simmons, JH, Fernandez-Duque, E, Kanthaswamy, S, Shiferaw, F, Wu, D, Zhou, L, Shao, Y
, Zhang, G, Keyyu, JD, Knauf, S, Le, MD, Lizano, E, Merker, S, Navarro, A, Bataillon, T, Nadler, T, Khor, CC, Lee, J, Tan, P, Lim, WK, Kitchener, AC, Zinner, D, Gut, I, Melin, A, Guschanski, K, Schierup, MH, Beck, RMD, Umapathy, G, Roos, C, Boubli, JP, Lek, M, Sunyaev, S, O'Donnell-Luria, A, Rehm, HL, Xu, J, Rogers, J, Marques-Bonet, T & Farh, KKH 2023, '
The landscape of tolerated genetic variation in humans and primates',
Science (New York, N.Y.), vol. 380, no. 6648.
https://doi.org/10.1126/science.abn8197APA
Gao, H., Hamp, T., Ede, J., Schraiber, J. G., McRae, J., Singer-Berk, M., Yang, Y., Dietrich, A. S. D., Fiziev, P. P., Kuderna, L. F. K., Sundaram, L., Wu, Y., Adhikari, A., Field, Y., Chen, C., Batzoglou, S., Aguet, F., Lemire, G., Reimers, R., ... Farh, K. K. H. (2023).
The landscape of tolerated genetic variation in humans and primates.
Science (New York, N.Y.),
380(6648).
https://doi.org/10.1126/science.abn8197Vancouver
Gao H, Hamp T, Ede J, Schraiber JG, McRae J, Singer-Berk M et al.
The landscape of tolerated genetic variation in humans and primates.
Science (New York, N.Y.). 2023;380(6648).
https://doi.org/10.1126/science.abn8197Author
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. / The landscape of tolerated genetic variation in humans and primates. In: Science (New York, N.Y.). 2023 ; Vol. 380, No. 6648.
Bibtex
@article{f6aba648f11248099446e7d47d9a6b0e,
title = "The landscape of tolerated genetic variation in humans and primates",
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.",
author = "Hong Gao and Tobias Hamp and Jeffrey Ede and Schraiber, {Joshua G.} and Jeremy McRae and Moriel Singer-Berk and Yanshen Yang and Dietrich, {Anastasia S.D.} and Fiziev, {Petko P.} and Kuderna, {Lukas F.K.} and Laksshman Sundaram and Yibing Wu and Aashish Adhikari and Yair Field and Chen Chen and Serafim Batzoglou and Francois Aguet and Gabrielle Lemire and Rebecca Reimers and Daniel Balick and Janiak, {Mareike C.} and Martin Kuhlwilm and Orkin, {Joseph D.} and Shivakumara Manu and Alejandro Valenzuela and Juraj Bergman and Marjolaine Rousselle and Silva, {Felipe Ennes} and Lidia Agueda and Julie Blanc and Marta Gut and {de Vries}, Dorien and Ian Goodhead and Harris, {R. Alan} and Muthuswamy Raveendran and Axel Jensen and Chuma, {Idriss S.} and Horvath, {Julie E.} and Christina Hvilsom and David Juan and Peter Frandsen and {de Melo}, {Fabiano R.} and Fabr{\'i}cio Bertuol and Hazel Byrne and Iracilda Sampaio and Izeni Farias and {do Amaral}, {Jo{\~a}o Valsecchi} and Mariluce Messias and {da Silva}, {Maria N.F.} and Mihir Trivedi and Rogerio Rossi and Tomas Hrbek and Nicole Andriaholinirina and Rabarivola, {Cl{\'e}ment J.} and Alphonse Zaramody and Jolly, {Clifford J.} and Jane Phillips-Conroy and Gregory Wilkerson and Christian Abee and Simmons, {Joe H.} and Eduardo Fernandez-Duque and Sree Kanthaswamy and Fekadu Shiferaw and Dongdong Wu and Long Zhou and Yong Shao and Guojie Zhang and Keyyu, {Julius D.} and Sascha Knauf and Le, {Minh D.} and Esther Lizano and Stefan Merker and Arcadi Navarro and Thomas Bataillon and Tilo Nadler and Khor, {Chiea Chuen} and Jessica Lee and Patrick Tan and Lim, {Weng Khong} and Kitchener, {Andrew C.} and Dietmar Zinner and Ivo Gut and Amanda Melin and Katerina Guschanski and Schierup, {Mikkel Heide} and Beck, {Robin M.D.} and Govindhaswamy Umapathy and Christian Roos and Boubli, {Jean P.} and Monkol Lek and Shamil Sunyaev and Anne O'Donnell-Luria and Rehm, {Heidi L.} and Jinbo Xu and Jeffrey Rogers and Tomas Marques-Bonet and Farh, {Kyle Kai How}",
year = "2023",
doi = "10.1126/science.abn8197",
language = "English",
volume = "380",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6648",
}
RIS
TY - JOUR
T1 - The landscape of tolerated genetic variation in humans and primates
AU - Gao, Hong
AU - Hamp, Tobias
AU - Ede, Jeffrey
AU - Schraiber, Joshua G.
AU - McRae, Jeremy
AU - Singer-Berk, Moriel
AU - Yang, Yanshen
AU - Dietrich, Anastasia S.D.
AU - Fiziev, Petko P.
AU - Kuderna, Lukas F.K.
AU - Sundaram, Laksshman
AU - Wu, Yibing
AU - Adhikari, Aashish
AU - Field, Yair
AU - Chen, Chen
AU - Batzoglou, Serafim
AU - Aguet, Francois
AU - Lemire, Gabrielle
AU - Reimers, Rebecca
AU - Balick, Daniel
AU - Janiak, Mareike C.
AU - Kuhlwilm, Martin
AU - Orkin, Joseph D.
AU - Manu, Shivakumara
AU - Valenzuela, Alejandro
AU - Bergman, Juraj
AU - Rousselle, Marjolaine
AU - Silva, Felipe Ennes
AU - Agueda, Lidia
AU - Blanc, Julie
AU - Gut, Marta
AU - de Vries, Dorien
AU - Goodhead, Ian
AU - Harris, R. Alan
AU - Raveendran, Muthuswamy
AU - Jensen, Axel
AU - Chuma, Idriss S.
AU - Horvath, Julie E.
AU - Hvilsom, Christina
AU - Juan, David
AU - Frandsen, Peter
AU - de Melo, Fabiano R.
AU - Bertuol, Fabrício
AU - Byrne, Hazel
AU - Sampaio, Iracilda
AU - Farias, Izeni
AU - do Amaral, João Valsecchi
AU - Messias, Mariluce
AU - da Silva, Maria N.F.
AU - Trivedi, Mihir
AU - Rossi, Rogerio
AU - Hrbek, Tomas
AU - Andriaholinirina, Nicole
AU - Rabarivola, Clément J.
AU - Zaramody, Alphonse
AU - Jolly, Clifford J.
AU - Phillips-Conroy, Jane
AU - Wilkerson, Gregory
AU - Abee, Christian
AU - Simmons, Joe H.
AU - Fernandez-Duque, Eduardo
AU - Kanthaswamy, Sree
AU - Shiferaw, Fekadu
AU - Wu, Dongdong
AU - Zhou, Long
AU - Shao, Yong
AU - Zhang, Guojie
AU - Keyyu, Julius D.
AU - Knauf, Sascha
AU - Le, Minh D.
AU - Lizano, Esther
AU - Merker, Stefan
AU - Navarro, Arcadi
AU - Bataillon, Thomas
AU - Nadler, Tilo
AU - Khor, Chiea Chuen
AU - Lee, Jessica
AU - Tan, Patrick
AU - Lim, Weng Khong
AU - Kitchener, Andrew C.
AU - Zinner, Dietmar
AU - Gut, Ivo
AU - Melin, Amanda
AU - Guschanski, Katerina
AU - Schierup, Mikkel Heide
AU - Beck, Robin M.D.
AU - Umapathy, Govindhaswamy
AU - Roos, Christian
AU - Boubli, Jean P.
AU - Lek, Monkol
AU - Sunyaev, Shamil
AU - O'Donnell-Luria, Anne
AU - Rehm, Heidi L.
AU - Xu, Jinbo
AU - Rogers, Jeffrey
AU - Marques-Bonet, Tomas
AU - Farh, Kyle Kai How
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1126/science.abn8197
DO - 10.1126/science.abn8197
M3 - Journal article
C2 - 37262156
AN - SCOPUS:85160969495
VL - 380
JO - Science
JF - Science
SN - 0036-8075
IS - 6648
ER -
