GPLEXUS: enabling genome-scale gene association network reconstruction and analysis for very large-scale expression data

The accurate construction and interpretation of gene association networks (GANs) is challenging, but crucial, to the understanding of gene function, interaction and cellular behavior at the genome level. Most current state-of-the-art computational methods for genome-wide GAN reconstruction require high-performance computational resources. However, even high-performance computing cannot fully address the complexity involved with constructing GANs from very large-scale expression profile datasets, especially for the organisms with medium to large size of genomes, such as those of most plant species. Here, we present a new approach, GPLEXUS (http://plantgrn.noble.org/GPLEXUS/), which integrates a series of novel algorithms in a parallel-computing environment to construct and analyze genome-wide GANs. GPLEXUS adopts an ultra-fast estimation for pairwise mutual information computing that is similar in accuracy and sensitivity to the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE) method and runs ~1000 times faster. GPLEXUS integrates Markov Clustering Algorithm to effectively identify functional subnetworks. Furthermore, GPLEXUS includes a novel ‘condition-removing’ method to identify the major experimental conditions in which each subnetwork operates from very large-scale gene expression datasets across several experimental conditions, which allows users to annotate the various subnetworks with experiment-specific conditions. We demonstrate GPLEXUS’s capabilities by construing global GANs and analyzing subnetworks related to defense against biotic and abiotic stress, cell cycle growth and division in Arabidopsis thaliana.