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Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans

Can Cenik, Elif Sarinay Cenik, Gun W. Byeon, Fabian Grubert, Sophie I Candille, Damek Spacek, Bilal Alsallakh, Hagen Tilgner, Carlos L. Araya, Hua Tang, Emiliano Ricci, Michael P. Snyder
doi: https://doi.org/10.1101/018572
Can Cenik
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Elif Sarinay Cenik
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Gun W. Byeon
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Fabian Grubert
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Sophie I Candille
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Damek Spacek
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Bilal Alsallakh
2Institute of Software Technology & Interactive Systems, Vienna University of Technology, Karlsplatz 13, Vienna, Austria
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Hagen Tilgner
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Carlos L. Araya
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Hua Tang
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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Emiliano Ricci
3RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA
4CIRI, International center for Infectiology Research, eukaryotic and viral translation team, Université de Lyon, INSERM U1111, Lyon, France
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Michael P. Snyder
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 94305
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  • For correspondence: mpsnyder@stanford.edu
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Abstract

Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy - many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 26, 2015.
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Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans
Can Cenik, Elif Sarinay Cenik, Gun W. Byeon, Fabian Grubert, Sophie I Candille, Damek Spacek, Bilal Alsallakh, Hagen Tilgner, Carlos L. Araya, Hua Tang, Emiliano Ricci, Michael P. Snyder
bioRxiv 018572; doi: https://doi.org/10.1101/018572
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Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans
Can Cenik, Elif Sarinay Cenik, Gun W. Byeon, Fabian Grubert, Sophie I Candille, Damek Spacek, Bilal Alsallakh, Hagen Tilgner, Carlos L. Araya, Hua Tang, Emiliano Ricci, Michael P. Snyder
bioRxiv 018572; doi: https://doi.org/10.1101/018572

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