Identification of Ribosome Pause Sites Using a Z-Score Based Peak Detection Algorithm

Abstract

During protein synthesis, the speed of ribosomes as they move along mRNAs can vary based on multiple biological factors. It has been reported that pausing of ribosomes can influence gene expression through multiple mechanisms, such as facilitating protein folding and triggering translational abandonment. However, a deeper understanding of ribosomal pausing and its’ regulation is still missing. Ribosome profiling is a rapidly emerging technique for capturing a global snap-shot of ribosome position and activity. The method shows great potential for investigating many aspects of translating ribosomes. In particular, pause sites can be found by identifying peaks in ribosome profiling data. Here we present riboSmoothR, a novel method for identifying such peaks. Our algorithm utilizes the smoothed z-score method to identify anomalous ribosome footprint counts along a transcript. We show that riboSmoothR identifies a larger number of conserved peak sites than other commonly used peak finding methods. Additionally, we describe sequence-based features associated with peak sites identified by our method, such as codon and amino acid biases.