RT Journal Article
SR Electronic
T1 Identifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 490755
DO 10.1101/490755
A1 Nabeel Ahmed
A1 Pietro Sormanni
A1 Prajwal Ciryam
A1 Michele Vendruscolo
A1 Christopher M Dobson
A1 Edward P O'Brien
YR 2018
UL http://biorxiv.org/content/early/2018/12/17/490755.abstract
AB 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 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 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.