Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus ‘metabolic reconstruction’, which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including ~2× more reactions and ~1.7× more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type–specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.

Mulliner, Emma and Malys, Naglis and Maliene, Vida (2016) A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. AbstractWhile affordability is traditionally assessed in economic terms, this paper tests a new assessment method that draws closer links with sustainability by considering economic, social and environmental criteria that impact on a household's quality of life. The paper presents an empirical application and comparison of six different multiple criteria decision making (MCDM) approaches for the purpose of assessing sustainable housing affordability.The comparative performance of the weighted product model (WPM), the weighted sum model (WSM), the revised AHP, TOPSIS and COPRAS, is investigated. The purpose of the comparative analysis is to determine how different MCDM methods compare when used for a sustainable housing affordability assessment model. 20 evaluative criteria and 10 alternative areas in Liverpool, England, were considered. The applicability of different MCDM methods for the focused decision problem was investigated. The paper discusses the similarities in MCDM methods, evaluates their robustness and contrasts the resulting rankings.

We present an experimental and computational pipeline for the generation of kinetic models of metabolism, and demonstrate its application to glycolysis in Saccharomyces cerevisiae. Starting from an approximate mathematical model, we employ a “cycle of knowledge” strategy, identifying the steps with most control over flux. Kinetic parameters of the individual isoenzymes within these steps are measured experimentally under a standardised set of conditions. Experimental strategies are applied to establish a set of in vivo concentrations for isoenzymes and metabolites. The data are integrated into a mathematical model that is used to predict a new set of metabolite concentrations and reevaluate the control properties of the system. This bottom-up modelling study reveals that control over the metabolic network most directly involved in yeast glycolysis is more widely distributed than previously thought.