PXD001406-2

PXD001406 is an original dataset announced via ProteomeXchange.

Title	Impact of Regulatory Variation from RNA to Protein
Description	Genetic variants that impact gene regulation are important contributors to human phenotypic variation. For this reason, considerable efforts have been made to identify genetic associations with differences in mRNA levels of nearby genes, namely, cis expression quantitative trait loci (eQTLs). The phenotypic consequences of eQTLs are presumably due, in most cases, to their ultimate effects on protein expression levels. Yet, only few studies have quantified the impact of genetic variation on proteins levels directly. It remains unclear how faithfully eQTLs are reflected at the protein level, and whether there is a significant layer of cis regulatory variation acting primarily on translation or steady state protein levels. To address these questions, we measured ribosome occupancy by high-throughput sequencing, and relative protein levels by high-resolution quantitative mass spectrometry, in a panel of lymphoblastoid cell lines (LCLs) in which we had previously measured transcript expression using RNA sequencing. We then mapped genetic variants that are associated with changes in transcript expression (eQTLs), ribosome occupancy (rQTLs), or protein abundance (pQTLs). Most of the QTLs we detected are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, we found that eQTLs tend to have significantly reduced effect sizes on protein levels, suggesting that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we confirmed the presence of a class of cis QTLs that specifically affect protein abundance with little or no effect on mRNA levels; most of these QTLs have little effect on ribosome occupancy, and hence may arise from differences in post-translational regulation.
HostingRepository	PRIDE
AnnounceDate	2017-06-20
AnnouncementXML	Submission_2017-06-20_05:42:57.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zia Khan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2014-10-17 00:22:07	ID requested
1	2014-12-19 06:55:53	announced
⏵ 2	2017-06-20 05:42:58	announced	Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: SILAC, genetic variation, HapMap, lymphoblastoid cell line, Ribosome profiling, RNA-seq, pQTL, eQTL, post-translational, gene regulation

Yoav Gilad
contact affiliation	Department of Human Genetics University of Chicago
contact email	gilad@uchicago.edu
lab head
Zia Khan
contact affiliation	University of Maryland College Park Center for Bioinformatics and Computational Biology Department of Computer Science
contact email	zia@cs.umd.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2014/12/PXD001406

PRIDE project URI

• PRIDE
  1. PXD001406
     1. Label: PRIDE project
     2. Name: Impact of Regulatory Variation from RNA to Protein