BRIDGE A: LIPID MAPS NETWORKSThe main objective of this Bridge Project is the reconstruction and modeling of lipidomic networks inmacrophages. In the first part of this objective, a combination of inference and statistical learning basedmethods will be used to reconstruct networks from lipid and gene expression data obtained by the LipidomicsCore laboratories of LIPID MAPS. The statistical learning approach includes use of principal componentregression and temporal analysis of modules. The LIPID MAPS project will also carry out experiments withstable isotope metabolite precursors. These include CIS-labeled arachidonate, acetate, palmitate, andmevalonate. Bridge A will develop quantitative methods for modeling and analysis of isotopomeric data andwill provide kinetic analyses of derived models. From the latter developments, it will be possible to designnovel experiments and conceive quantitative hypotheses to predict the consequences of pharmacological andgenetic perturbations on lipid networks. In addition, the isotopomer data will be used to elucidate pathways ofcatabolism versus anabolism of lipids.Unlike protein networks, little is known about the lipid networks of mammalian cells. Development of lipidnetworks requires a systems biology approach involving large scale measurements of network playersfollowed by mathematically intensive integrative analyses of the data to develop interaction models. Thesemodels serve as frameworks for understanding cellular function in normal and pathological conditions. BridgeA will lead the development of new methods for reconstruction and modeling of lipid networks and will providethe scientific community with tools for pathway-based approaches to study cellular function.
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