PT  - JOURNAL ARTICLE
AU  - Khanh Dao Duc
AU  - Zain H. Saleem
AU  - Yun S. Song
TI  - Theoretical quantification of interference in the TASEP: application to mRNA translation shows near-optimality of termination rates
AID  - 10.1101/147017
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 147017
4099  - http://biorxiv.org/content/early/2017/06/07/147017.short
4100  - http://biorxiv.org/content/early/2017/06/07/147017.full
AB  - The Totally Asymmetric Exclusion Process (TASEP) is a classical stochastic model for describing the transport of interacting particles, such as ribosomes moving along the mRNA during translation. Applying this model to quantify translation dynamics from ribosome profiling data is not straightforward, however, and it requires characterizing the extent of interference, since the experimental protocol may be biased against nearby ribosomes. To evaluate and correct for this potential bias, we provide here a theoretical analysis of the distribution of isolated particles in the TASEP. In the classical form of the model in which each particle occupies only a single site, we obtain exact analytic solutions using the Matrix Ansatz. We then employ a refined mean field approach to extend the analysis to a generalized TASEP with particles of an arbitrary size. Our theoretical study has direct applications in mRNA translation and the interpretation of experimental ribosome profiling data. In particular, our analysis of data from S. cerevisiae suggests a potential bias against the detection of nearby ribosomes with gap distance less than ~ 3 codons, which leads to some ambiguity in estimating the initiation rate and protein production flux for a substantial fraction of genes. Despite such ambiguity, however, we demonstrate theoretically that the interference rate can be robustly estimated, and show that approximately 1% of the translating ribosomes get obstructed. Lastly, we find that, on average, the termination rate is near optimal in that it is close to the minimum value needed to not limit the ribosome flux.