Identifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming

Nabeel Ahmed, Pietro Sormanni, Prajwal Ciryam, Michele Vendruscolo, Christopher M. Dobson, Edward P. O’Brien

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Abstract

Identifying the A- and P-site locations on ribosome-protected mRNA fragments from Ribo-Seq experiments is a fundamental step in the quantitative analysis of transcriptome-wide translation properties at the codon level. Many analyses of Ribo-Seq data have utilized heuristic approaches applied to a narrow range of fragment sizes to identify the A-site. In this study, we use Integer Programming to identify the A-site by maximizing an objective function that reflects the fact that the ribosome’s A-site on ribosome-protected fragments must reside between the second and stop codons of an mRNA. This identifies the A-site location as a function of the fragment’s size and its 5′ end reading frame in Ribo-Seq data generated from S. cerevisiae and mouse embryonic stem cells. The correctness of the identified A-site locations is demonstrated by showing that this method, as compared to others, yields the largest ribosome density at established stalling sites. By providing greater accuracy and utilization of a wider range of fragment sizes, our approach increases the signal-to-noise ratio of underlying biological signals associated with translation elongation at the codon length scale.

Original languageEnglish (US)
Article number6256
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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All Science Journal Classification (ASJC) codes

  • General

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