Discovery of gene network variability across samples representing multiple classes

Abstract

Gene networks have been predicted using the expression profiles from microarray experiments that include multiple samples representing each of several classes or states (e.g., treatments, developmental stages, health status). A framework that integrates Bayesian networks, mixture of gene co-expression models and clustering is proposed to further mine information from the variation of samples within and across classes and enhance the understanding of gene networks. The approach was evaluated on two independent pathways using data from two microarray experiments. Our algorithm succeeded on reconstructing the topology of the gene pathways when benchmarked against empirical reports and randomised data sets. The majority or all the samples within a class shared the same co-expression model and were classified within the corresponding class. Our approach uncovered both gene relationships and profiles that are unique to a particular class or shared across classes.

Figure 1

Comparison of the predicted and expected relationships between genes pertaining to the starch and sucrose metabolism pathway. Note: Solid arrows denote direct relationships predicted by the Bayesian network approach encompassing multiple co-expression models and confirmed in the fruit fly KEGG starch and sucrose metabolism pathway. Dashed arrows represent indirect relationships predicted and confirmed in the KEGG pathway. Dashed-dot arrows represent a predicted relationships that is found in the KEGG pathway with opposite direction. Genes: sgl = sugarless; abs = abstract; CG15117 = beta-glucuronidase; Amy-p = Amylase proximal; Hex-A = Hexokinase A; Tps1 = Trehalose-6-phosphate synthase 1; CG10333 = DmRH19; UGP = UTP-glucose-1-phsphate uridylyltransferase; Ugt86Dg = Glucuronosyltransferase; GlyP = Glycogen phosphorylase.

Figure 2

Distribution of the 60 honey bee samples and classes across the first three principal components that explained 96% of the variation of the co-expression patterns of the 10 genes in the starch and sucrose metabolism pathway studied. Note : OF: Old Forager, TF: Traditional Forager, YF: Young Forager, ON: Old Nurse, TN: Traditional Nurse and YN: Young Nurse.

Figure 3

Comparison of the predicted and expected relationships between genes in the circadian rhythm pathway. Note : Solid arrows denote direct relationships predicted by the Bayesian network approach encompassing multiple co-expression models and confirmed in the fruit fly KEGG circadian rhythm pathway. Dashed arrows represent indirect relationships predicted and confirmed in the KEGG pathway. Genes: Vri = vrille; Pdp = PAR-domain protein 1; Sgg = shaggy; Per = period; Dbt = Casein kinase I alpha