Reconstruction of genome-scale metabolic models for 126 human tissues using mCADRE

We developed a method called metabolic Context-specificity Assessed by Deterministic Reaction Evaluation (mCADRE). mCADRE is able to infer a tissue-specific network based on gene expression data and metabolic network topology, along with evaluation of functional capabilities during model building. mCADRE produces models with similar or better functionality and achieves dramatic computational speed up over existing methods. Using our method, we reconstructed draft genome-scale metabolic models for 126 human tissue and cell types. Among these, there are models for 26 tumor tissues along with their normal counterparts, and 30 different brain tissues. We performed pathway-level analyses of this large collection of tissue-specific models and identified the eicosanoid metabolic pathway, especially reactions catalyzing the production of leukotrienes from arachidnoic acid, as potential drug targets that selectively affect tumor tissues.This large collection of 126 genome-scale draft metabolic models provides a useful resource for studying the metabolic basis for a variety of human diseases across many tissues. The functionality of the resulting models and the fast computational speed of the mCADRE algorithm make it a useful tool to build and update tissue-specific metabolic models.Metabolic dysfunction has been implicated in a wide variety of human diseases such as obesity, diabetes, inborn errors of metabolism, neurodegenerative diseases, and cancer. The recent reconstruction of genome-scale models of human metabolism [1,2] provides an important biochemical basis for systems analysis of metabolic related aspects of human physiology and pathology [3]. Such systems approaches are critical, as metabolism itself is a molecular transformation process where numerous metabolic pathways are inextricably interlinked [4]. However, the human body consists of many distinct tissues and cell types, each only expressing a fraction of the metabolic genes encoded within the genome [5]. Add