Initiation probability is randomly determined from a mean value and a value that determines the variability around the mean, implemented so that the log of the initiation probability is normally distributed.
An initiation probability of 0.05, for example, means that an origin has a 5% probability of firing in a time step.
In the initiation stage, a random test is performed on each licensed origin, based on its initiation probability, to determine whether it will initiate.
Each origin was also assigned an initiation probability.
JBOriginController performs a random test on each licensed origin based on its initiation probability.
Each JBOrigin contains information about its location, initiation probability and status (licensed/fired/passively replicated).
In the simulations above, we set the initiation probability of the transgene at the 95th percentile of endogenous initiation probabilities because transgenes are typically optimized for rapid initiation (Salis et al., 2009; Welch et al., 2009).
In all the experiments shown here, the initiation probabilities of individual origins were distributed around a specified mean value (see Methods), meaning that within one cluster different origins have higher or lower initiation probabilities.
We validated that our analytical method can indeed reliably infer initiation probabilities when we simulate ribosome profiling data for S. cerevisiae genes with known initiation probabilities.
In addition, we validated that we can reliably infer initiation probabilities from simulated ribosomal profiling data even when gene length and initiation probabilities are positively correlated.
