Journal
JOURNAL OF COMPUTATIONAL BIOLOGY
Volume 24, Issue 6, Pages 486-500Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/cmb.2016.0147
Keywords
A-site recovery; ribosome profiling; translation rate
Categories
Funding
- Gordon and Betty Moore Foundation's Data-Driven Discovery Initiative [GBMF4554]
- U.S. National Science Foundation [CCF-1256087, CCF-1319998]
- U.S. National Institutes of Health [R21HG006913, R01HG007104]
- Direct For Computer & Info Scie & Enginr
- Division of Computing and Communication Foundations [1256087] Funding Source: National Science Foundation
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Ribosome profiling quantitatively captures ribosome locations during translation. The resulting profiles of ribosome locations are widely used to study translational speed. However, an accurate estimation of the ribosome location depends on identifying the A-site from ribosome profiling reads, a problem that was previously unsolved. Here, we propose a novel method to estimate the ribosome A-site positions from high-coverage ribosome profiling reads. Our model allows more reads to be used, accurately explains the 3-nt periodicity of ribosome profiling reads from various lengths, and recovers consistent ribosome positions across different lengths. Our recovered ribosome positions are correctly highly skewed toward a single frame within a codon. They retain subcodon resolution and enable detection of off-frame translational events, such as frameshifts. Our method improves the correlation with other estimates of codon decoding time. Furthermore, the refined profiles show that yeast wobble-pairing codons are translated slower than their synonymous Watson-Crick-pairing codons. These results provide evidence that protein synthetic rate can be tuned by codon usage bias.
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