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bioRxiv · 10.1101/490755

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

Ahmed, N.·Sormanni, P.·Ciryam, P.·Vendruscolo, M.·Dobson, C. M.·O'Brien, E. P.
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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 A-site by maximizing an objective function that reflects the fact that the ribosomes 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 fragments size and its 5{square} 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.

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Ahmed, N., Sormanni, P., Ciryam, P., Vendruscolo, M., Dobson, C. M., O'Brien, E. P.. 2018-12-17. Identifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming. https://doi.org/10.1101/490755

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