Modeling regulatory networks with weight matrices.
Systematic gene expression analyses provide comprehensive information about the transcriptional response to different environmental and developmental conditions. With enough gene expression data points, computational biologists may eventually generate predictive computer models of transcription regulation. Such models will require computational methodologies consistent with the behavior of known biological systems that remain tractable. We represent regulatory relationships between genes as linear coefficients or weights, with the "net" regulation influence on a gene's expression being the mathematical summation of the independent regulatory inputs. Test regulatory networks generated with this approach display stable and cyclically stable gene expression levels, consistent with known biological systems. We include variables to model the effect of environmental conditions on transcription regulation and observed various alterations in gene expression patterns in response to environmental input. Finally, we use a derivation of this model system to predict the regulatory network from simulated input/output data sets and find that it accurately predicts all components of the model, even with noisy expression data.
Weaver
D C
DC
Genomica Corporation, Boulder, CO 80303, USA. weaver@genomica.com
Workman
C T
CT
Stormo
G D
GD
D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D016208:Databases, Factual; D004777:Environment; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D008957:Models, Genetic; D015203:Reproducibility of Results; D012984:Software; D014158:Transcription, Genetic