Deterministic and stochastic descriptions of gene expression dynamics

A key goal of systems biology is the predictive mathematical description of gene regulatory circuits. Different approaches are used such as deterministic and stochastic models, models that describe cell growth and division explicitly or implicitly etc. Here we consider simple systems of unregulated (constitutive) gene expression and compare different mathematical descriptions systematically to obtain insight into the errors that are introduced by various common approximations such as describing cell growth and division by an effective protein degradation term. In particular, we show that the population average of protein content of a cell exhibits a subtle dependence on the dynamics of growth and division, the specific model for volume growth and the age structure of the population. Nevertheless, the error made by models with implicit cell growth and division is quite small. Furthermore, we compare various models that are partially stochastic to investigate the impact of different sources of (intrinsic) noise. This comparison indicates that different sources of noise (protein synthesis, partitioning in cell division) contribute comparable amounts of noise if protein synthesis is not or only weakly bursty. If protein synthesis is very bursty, the burstiness is the dominant noise source, independent of other details of the model. Finally, we discuss two sources of extrinsic noise: cell-to-cell variations in protein content due to cells being at different stages in the division cycles, which we show to be small (for the protein concentration and, surprisingly, also for the protein copy number per cell) and fluctuations in the growth rate, which can have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012

An analysis of the creatine kinase isoenzyme and cardiac troponin T levels in a polymyositis patient

From an extensive model developed to interpret physiological processes we are able to show that the observed elevated creatine kinase-myoglobin (CK-MB) and serum concentration of cardiac troponin T (cTnT) values for a particular patient are associated with the inflammatory disease, polymyositis, and not myocardial injury. This highlights that caution must be exercised in using elevated CK-MB and cTnT levels as evidence for myocardial damage in patients with chronic muscle degeneration such as polymyositis

Polymyostis initiation involving amlodipine besylate

[Extract] Based on extensive blood pressure data and results from a scientific model of the analysis of the rate processes involved in polymyositis the evidence suggests that the polymyositis in a particular patient was initiated by taking the drug amlodipine besylate (norvasc). The method of our analysis should serve as a foundation in handling other drug related interactions