Codes for Weber et al, Physical Biology, 2018

This directory contains all codes needed to reproduce the results of the paper:

L. Weber, W Raymond, B. Munsky, "Identification of Gene regulation models from single-cell data," Physical Biology, 2018 (see abstract below).

The repository contains two folders. Matlab_Codes -- Contains all codes needed to reproduce the figures and analyses described in the manuscript. GUI -- Contains a Python-based GUI that can also be used to reproduce the results described in the manuscript.

Article Abstract: In quantitative analyses of biological processes, one may use many different scales of models (e.g., spatial or non-spatial, deterministic or stochastic, time-varying or at steady-state) or many different approaches to match models to experimental data (e.g., model fitting or parameter uncertainty/sloppiness quantification with different experiment designs). These different analyses can lead to surprisingly different results, even when applied to the same data and the same model. We use a simplified gene regulation model to illustrate many of these concerns, especially for ODE analyses of deterministic processes, chemical master equation and finite state projection analyses of heterogeneous processes, and stochastic simulations. For each analysis, we employ Matlab and Python software to consider a time-dependent input signal (e.g., a kinase nuclear translocation) and several model hypotheses, along with simulated single-cell data. We illustrate different approaches (e.g., deterministic and stochastic) to identify the mechanisms and parameters of the same model from the same simulated data. For each approach, we explore how uncertainty in parameter space varies with respect to the chosen analysis approach or specific experiment design. We conclude with a discussion of how our simulated results relate to the integration of experimental and computational investigations to explore signal-activated gene expression models in yeast (Neuert et al, 2013) and human cells (Senecal et al, 2014).

Questions or comments on the article or these codes should be addressed to Brian Munsky at munsky@colostate.edu.