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Series GSE69047 Query DataSets for GSE69047
Status Public on May 18, 2017
Title Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Ribosome profiling is a widespread tool for studying translational dynamics in human cells. Its central assumption is that ribosome footprint density on a transcript quantitatively reflects protein synthesis. Here, we test this assumption using pulsed-SILAC (pSILAC) high-accuracy targeted proteomics. We focus on multiple myeloma cells exposed to bortezomib, a first-line chemotherapy and proteasome inhibitor. In the absence of drug effects, we found that direct measurement of protein synthesis by pSILAC correlated well with indirect measurement of synthesis from ribosome footprint density. This correlation, however, broke down under bortezomib-induced stress. By developing a statistical model integrating longitudinal proteomic and mRNA-seq measurements, we found that proteomics could directly detect global alterations in translational rate caused by bortezomib; these changes are not detectable by ribosomal profiling alone. Further, by incorporating pSILAC data into a gene expression model, we predict cell-stress specific proteome remodeling events. These results demonstrate that pSILAC provides an important complement to ribosome profiling in measuring proteome dynamics.
Overall design Timecourse experiment with six points over 48hr after bortezomib exposure in MM.1S myeloma cells. mRNA-seq and ribosome profiling data at each time point.
Contributor(s) Liu T, Huang HH, Wheeler D, Xu Y, Wells JA, Song YS, Wiita AP
Citation(s) 28578850
NIH grant(s)
Grant ID Grant title Affiliation Name
K08 CA184116 Global Assessment of Myeloma Response to Chemotherapy University of California San Francisco Arun P. Wiita
Submission date May 19, 2015
Last update date May 15, 2019
Contact name Arun P. Wiita
Organization name University of California, San Francisco
Department Laboratory Medicine
Street address 185 Berry St., Suite 290
City San Francisco
State/province CA
ZIP/Postal code 94107
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (12)
GSM1691196 0h mRNA-seq data
GSM1691197 6h mRNA-seq data
GSM1691198 12h mRNA-seq data
BioProject PRJNA284399
SRA SRP058501

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Supplementary file Size Download File type/resource
GSE69047_mRNA-seq_and_footprint_reads_timecourse.xlsx 1.3 Mb (ftp)(http) XLSX
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