Motifs are repeating patterns that determine the local properties of networks. In this work, we characterized all 3-node motifs using enzyme commission numbers of the International Union of Biochemistry and Molecular Biology to show that motif abundance is related to biochemical function. Further, we present a comparative analysis of motif distributions in the metabolic networks of 21 species across six kingdoms of life. We found the distribution of motif abundances to be similar between species, but unique across cellular organelles. Finally, we show that motifs are able to capture inter-species differences in metabolic networks and that molecular differences between some biological species are reflected by the distribution of motif abundances in metabolic networks.

The present study was designed to examine the effects of short-term diet and exercise on markers of metabolic health, serum-stimulated production of inflammatory biomarkers from cultured monocytes and adipocytes, and serum lipomics. Twenty-one overweight/obese children (9 boys and 12 girls, age 13.0 ± 0.5 yr, BMI 33.0 ± 1.8 kg/m2) were placed on a 2-wk ad libitum, high-fiber, low-fat diet and daily exercise regimen. Fasting serum samples were taken pre- and postintervention for determination of cytokines, metabolic risk markers, and lipomics. Monocytes and adipocytes were incubated with pre- and postintervention serum to investigate changes in cytokine secretion. Correlative associations were calculated, followed by hierarchical clustering to determine relationships between fatty acid (FA) species and clinical biomarkers. Despite remaining overweight/obese, interleukin (IL)-6, IL-8, TNFα, PAI-1, resistin, amylin, leptin, insulin, and IL-1ra decreased and adiponectin increased. Culture studies indicated decreases in monocyte secretion of IL-6, TNFα, and IL-1β and adipocyte secretion of IL-6. Lipomic analysis revealed a decrease in total lipids and decreases in saturated FAs and an increase in 18:1/18:0. In general, Pearson's correlations revealed that inflammatory markers are negatively associated with a cluster of polyunsaturated FAs and positively correlated with several saturated FAs. These results indicate significant modification of multiple indices of metabolic health with short-term rigorous lifestyle modification in overweight/obese children prior to obesity reversal.

Phylogenetic trees are typically constructed using genetic and genomic data, and provide robust evolutionary relationships of species from the genomic point of view. We present an application of network motif mining and analysis of metabolic pathways that when used in combination with phylogenetic trees can provide a more complete picture of evolution. By using distributions of three-node motifs as a proxy for metabolic similarity, we analyze the ancestral origin of Eukaryotic organelles from the metabolic point of view to illustrate the application of our motif mining and analysis network approach. Our analysis suggests that the hypothesis of an early proto-Eukaryote could be valid. It also suggests that a δ- or ε-Proteobacteria may have been the endosymbiotic partner that gave rise to modern mitochondria. Our evolutionary analysis needs to be extended by building metabolic network reconstructions of species from the phylum Crenarchaeota, which is considered to be a possible archaeal ancestor of the eukaryotic cell. In this paper, we also propose a methodology for constructing phylogenetic trees that incorporates metabolic network signatures to identify regions of genomically-estimated phylogenies that may be spurious. We find that results generated from our approach are consistent with a parallel phylogenetic analysis using the method of feature frequency profiles.