Eigengene networks for studying the relationships between co-expression modules.
BACKGROUND
There is evidence that genes and their protein products are organized into functional modules according to cellular processes and pathways. Gene co-expression networks have been used to describe the relationships between gene transcripts. Ample literature exists on how to detect biologically meaningful modules in networks but there is a need for methods that allow one to study the relationships between modules.


RESULTS
We show that network methods can also be used to describe the relationships between co-expression modules and present the following methodology. First, we describe several methods for detecting modules that are shared by two or more networks (referred to as consensus modules). We represent the gene expression profiles of each module by an eigengene. Second, we propose a method for constructing an eigengene network, where the edges are undirected but maintain information on the sign of the co-expression information. Third, we propose methods for differential eigengene network analysis that allow one to assess the preservation of network properties across different data sets. We illustrate the value of eigengene networks in studying the relationships between consensus modules in human and chimpanzee brains; the relationships between consensus modules in brain, muscle, liver, and adipose mouse tissues; and the relationships between male-female mouse consensus modules and clinical traits. In some applications, we find that module eigengenes can be organized into higher level clusters which we refer to as meta-modules.


CONCLUSIONS
Eigengene networks can be effective and biologically meaningful tools for studying the relationships between modules of a gene co-expression network. The proposed methods may reveal a higher order organization of the transcriptome. R software tutorials, the data, and supplementary material can be found at the following webpage: http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/EigengeneNetwork.
Langfelder
Peter
P
Department of Human Genetics and Department of Biostatistics, University of California, Los Angeles, CA 90095, USA. peter.langfelder@gmail.com
Horvath
Steve
S
D000818:Animals; D001921:Brain / Q000378:metabolism; D003198:Computer Simulation; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D051379:Mice; D008957:Models, Genetic; D002679:Pan troglodytes; D013045:Species Specificity; D049490:Systems Biology; D014018:Tissue Distribution