Transcriptional processes: Models and inference

Abstract

Many biochemical events involve multistep reactions. One of the most important biological processes that involve multistep reaction is the transcriptional process. Models for multistep reaction necessarily need multiple states and it is a challenge to compute model parameters that best agree with experimental data. Therefore, the aim of this work is to design a multistep promoter model which accurately characterizes transcriptional bursting and is consistent with observed data. To address this issue, we develop a model for promoters with several OFF states and a single ON state using Erlang distribution. To explore the combined effects of model and data, we combine Monte Carlo extension of Expectation Maximization (MCEM) and delay Stochastic Simulation Algorithm (DSSA) and call the resultant algorithm as delay Bursty MCEM. We apply this algorithm to time-series data of endogenous mouse glutaminase promoter to validate the model assumptions and infer the kinetic parameters. Our results show that with multiple OFF states, we are able to infer and produce a model which is more consistent with experimental data. Our results also show that delay Bursty MCEM inference is more efficient.