Modeling the temporal evolution of the Drosophila gene expression from DNA microarray time series.
The time evolution of gene expression across the developmental stages of the host organism can be inferred from appropriate DNA microarray time series. Modeling this evolution aims eventually at improving the understanding and prediction of the complex phenomena that are the basis of life. We focus on the embryonic-to-adult development phases of Drosophila melanogaster, and chose to model the expression network with the help of a system of differential equations with constant coefficients, which are nonlinear in the transcript concentrations but linear in their logarithms. To reduce the dimensionality of the problem, genes having similar expression profiles are grouped into 17 clusters. We show that a simple linear model is able to reproduce the experimental data with very good precision, owing to the large number of parameters that represent the connections between the clusters. Remarkably, the parameter reduction allowed elimination of up to 80-85% of these connections while keeping fairly good precision. This result supports the low-connectivity hypothesis of gene expression networks, with about three connections per cluster, without introducing a priori hypotheses. The core of the network shows a few gene clusters with negative self-regulation, and some highly connected clusters involving proteins with crucial functions.
Haye
Alexandre
A
Unité de Bioinformatique Génomique et Structurale, CP 165/61, Université Libre de Bruxelles, Avenue Roosevelt 50, 1050 Bruxelles, Belgium. ahaye@ulb.ac.be
Dehouck
Yves
Y
Kwasigroch
Jean Marc
JM
Bogaerts
Philippe
P
Rooman
Marianne
M
D000465:Algorithms; D000818:Animals; D016000:Cluster Analysis; D004330:Drosophila / Q000235:genetics*; D019143:Evolution, Molecular; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis