Estimation of peptide elongation times from ribosome profiling spectra.
Michael Y PavlovGustaf UllmanZoya IgnatovaMåns EhrenbergPublished in: Nucleic acids research (2021)
Ribosome profiling spectra bear rich information on translation control and dynamics. Yet, due to technical biases in library generation, extracting quantitative measures of discrete translation events has remained elusive. Using maximum likelihood statistics and data set from Escherichia coli we develop a robust method for neutralizing technical biases (e.g. base specific RNase preferences in ribosome-protected mRNA fragments (RPF) generation), which allows for correct estimation of translation times at single codon resolution. Furthermore, we validated the method with available datasets from E. coli treated with antibiotic to inhibit isoleucyl-tRNA synthetase, and two datasets from Saccharomyces cerevisiae treated with two RNases with distinct cleavage signatures. We demonstrate that our approach accounts for RNase cleavage preferences and provides bias-corrected translation times estimates. Our approach provides a solution to the long-standing problem of extracting reliable information about peptide elongation times from highly noisy and technically biased ribosome profiling spectra.
Keyphrases
- escherichia coli
- saccharomyces cerevisiae
- single cell
- density functional theory
- rna seq
- dna binding
- health information
- decision making
- gene expression
- mass spectrometry
- single molecule
- dna methylation
- healthcare
- machine learning
- dengue virus
- zika virus
- molecular dynamics
- social media
- biofilm formation
- cystic fibrosis
- artificial intelligence