Dynamic measure of gene co-regulation.
Gene expression is to a large extent controlled at the level of mRNA accumulation. Genes whose products function together are likely under a common regulatory system (e.g., signal transduction pathways, sets of regulatory proteins) such that they are expressed in a coordinated manner. This property has been frequently used in the analysis of genome-wide expression data, as the experimental observation that a group of genes is co-expressed frequently implies that the genes share a common regulatory mechanism. The authors have investigated the situation in which dissimilarity in gene-expression time profiles may still result from the presence of the same regulatory signal, as in the case of common transcription factors. To this aim, a dynamic model that takes into account the effect of specific mRNA degradation on the shape of gene-expression time series has been developed, and the concept of 'dynamically co-regulated' genes has accordingly been introduced as the goodness-of-fit to such a model (called dynamic R2). The statistical analysis of dynamic R2 over a number of different experimental data sets and organisms shows that the presence of dynamically co-regulated genes is by far more significant than that expected from the randomised data. Furthermore, as an example of the usefulness of the proposed method, genome-wide yeast measurements such as cell-cycle time series and transcription factors targets data, were used to prove that dynamic co-regulation is statistically related to the presence of common transcription factor(s). This latter property is very useful when trying to infer computational indications of co-regulation for not-yet annotated genes that do not display a co-expression pattern.
Farina
L
L
Dipartimento di Informatica e Sistemistica Antonio Ruberti, Università di Roma La Sapienza, Via Eudossiana 18, Rome 00184, Italy. lorenzo.farina@uniroma1.it
De Santis
A
A
Morelli
G
G
Ruberti
I
I
D002453:Cell Cycle / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling / Q000706:statistics & numerical data*; D005786:Gene Expression Regulation / Q000235:genetics*; D016681:Genome, Fungal; D015233:Models, Statistical; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D049490:Systems Biology / Q000379:methods*; D015003:Yeasts / Q000235:genetics
D012333:RNA, Messenger