de Jong S et al. BMC Genomics 2010, 11:20 http://www.biomedcentral.com/1471-2164/11/20 Page 8 of 14 approach reconstructs networks of genes with related expression profiles that are thought to represent biologi- cal meaningful correlations. Reconstruction of these modules is performed in an unbiased fashion, indepen- dent of strain or tissue origin. These results may provide new insights or complement our existing knowledge on brain region-specific molecular pathways. Since the hip- pocampus and amygdala are largely conserved between man and mouse, and are thought to play an important role in behavior, emotion and cognition, studying these brain regions may aid our understanding of mechanisms underlying neuropsychiatric traits. We observed differential expression between A/J and C57BL/6J mouse inbred strains and between the amyg- dala versus hippocampus brain regions (Figure 3). Further analysis demonstrated that differences in gene expression profiles between brain tissues were indepen- dent of strain origin (Figure 2, Additional File 4). While we provide evidence that the observed strain-specific dif- ferences are likely the result of hybridization artifacts (i.e. Magenta module), we postulate that networks enriched with genes that are differentially expressed between amygdala and hippocampus (i.e. Pink and Red modules) represent biological relevant molecular pathways. A lim- itation of our study is that both hippocampus and amyg- dala are not homogeneous (see for example [37,38]). Future research could aim to further dissect these regions (e.g. by laser capture) so that more homogenous sub- regions could be studied. Our study provides a more glo- bal assessment of differential expression between these large brain structures thereby ignoring the regional sub- structures within each of the brain regions. Figure 5 Visual representation of connections of genes in Red module. This figure shows target genes of the probes in the Red module with the strongest connections only (r > 0.92). Circles (○) denote genes with increased expression levels in hippocampus and diamonds (◊) represent genes with increased expression levels in the amygdala. Node size is related to the number of connections of that particular gene; a highly connected gene (i.e. ‘hub gene’) is therefore larger than genes with fewer connections. Nodes are colored blue when they appear in the Ingenuity categories Neurological Disease, Genetic Disorder and Psychological Disorder. Green nodes represent the genes unique to the Genetic Disorder category. Edge length is not related to correlation strength.