Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum

In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurable metabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source during rehydration.The functional module identifies relationships among changed metabolites (e.g. spermidine) and reactions and provides first insights into important altered metabolic pathways. With sparse and diverse data available, the presented integrated metabolite network approach is suitable to integrate all existing data and analyse it in a combined manner.Tardigrades are multicellular organisms, resistant to extreme environmental changes including desiccation, freezing and radiation. They outlast these conditions in an inactive form, called tun state or cryptobiosis [1-4]. All metabolic activity decreases during tun formation up to a complete cessation of measurable metabolism until environmental conditions improve and the tardigrade returns to its active state (see Figure 1). Other invertebrate taxa that undergo cryptobiosis to escape damage to cellular structures and cell