RT Journal
A1 Cenik, Can
A1 Sarinay Cenik, Elif
A1 Byeon, Gun W
A1 Grubert, Fabian
A1 Candille, Sophie I
A1 Spacek, Damek
A1 Alsallakh, Bilal
A1 Tilgner, Hagen
A1 Araya, Carlos L
A1 Tang, Hua
A1 Ricci, Emiliano
A1 Snyder, Michael P
T1 Integrative analysis of RNA, translation and protein levels reveals distinct regulatory variation across humans
JF Genome Research 
JO Genome Research 
YR 2015 
FD August 21 
DO 10.1101/gr.193342.115 
SP gr.193342.115 
UL http://genome.cshlp.org/content/early/2015/08/21/gr.193342.115.abstract 
AB 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.