Genome-wide identification and differential analysis of translational initiation

Nat Commun. 2017 Nov 23;8(1):1749. doi: 10.1038/s41467-017-01981-8.

Abstract

Translation is principally regulated at the initiation stage. The development of the translation initiation (TI) sequencing (TI-seq) technique has enabled the global mapping of TIs and revealed unanticipated complex translational landscapes in metazoans. Despite the wide adoption of TI-seq, there is no computational tool currently available for analyzing TI-seq data. To fill this gap, we develop a comprehensive toolkit named Ribo-TISH, which allows for detecting and quantitatively comparing TIs across conditions from TI-seq data. Ribo-TISH can also predict novel open reading frames (ORFs) from regular ribosome profiling (rRibo-seq) data and outperform several established methods in both computational efficiency and prediction accuracy. Applied to published TI-seq/rRibo-seq data sets, Ribo-TISH uncovers a novel signature of elevated mitochondrial translation during amino-acid deprivation and predicts novel ORFs in 5'UTRs, long noncoding RNAs, and introns. These successful applications demonstrate the power of Ribo-TISH in extracting biological insights from TI-seq/rRibo-seq data.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • 5' Untranslated Regions / genetics*
  • Computational Biology
  • Gene Library
  • Genome, Human
  • HEK293 Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Models, Statistical
  • Open Reading Frames
  • Peptide Chain Initiation, Translational / genetics*
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Sequence Analysis, RNA

Substances

  • 5' Untranslated Regions
  • RNA, Long Noncoding
  • RNA, Messenger