title: A robust and efficient method for estimating enzyme complex abundance and metabolic flux from expression data.
abstract: A major theme in constraint-based modeling is unifying experimental data, such as biochemical information about the reactions that can occur in a system or the composition and localization of enzyme complexes, with high-throughput data including expression data, metabolomics, or DNA sequencing. The desired result is to increase predictive capability and improve our understanding of metabolism. The approach typically employed when only gene (or protein) intensities are available is the creation of tissue-specific models, which reduces the available reactions in an organism model, and does not provide an objective function for the estimation of fluxes. We develop a method, flux assignment with LAD (least absolute deviation) convex objectives and normalization (FALCON), that employs metabolic network reconstructions along with expression data to estimate fluxes. In order to use such a method, accurate measures of enzyme complex abundance are needed, so we first present an algorithm that addresses quantification of complex abundance. Our extensions to prior techniques include the capability to work with large models and significantly improved run-time performance even for smaller models, an improved analysis of enzyme complex formation, the ability to handle large enzyme complex rules that may incorporate multiple isoforms, and either maintained or significantly improved correlation with experimentally measured fluxes. FALCON has been implemented in MATLAB and ATS, and can be downloaded from: https://github.com/bbarker/FALCON. ATS is not required to compile the software, as intermediate C source code is available. FALCON requires use of the COBRA Toolbox, also implemented in MATLAB.
authors.affiliation: Center for Advanced Computing, Cornell University, 534 Rhodes Hall, Ithaca, NY, USA.
authors.forename: Brandon E
authors.initials: BE
authors.lastname: Barker
authors.affiliation: Program of Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, USA.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Sadagopan
authors.affiliation: Tri-Institutional Training Program in Computational Biology and Medicine, 1300 York Avenue, Box 194, New York, NY, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Computer Science, The University of Manchester, Manchester, UK.|Manchester Center for Integrative Systems Biology, The University of Manchester, Manchester, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Smallbone
authors.affiliation: Tri-Institutional Training Program in Computational Biology and Medicine, 1300 York Avenue, Box 194, New York, NY, USA.|Laboratory of Atomic and Solid State Physics, Cornell University, Ithaca, NY, USA.|Institute of Biotechnology, Cornell University, Ithaca, NY, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Myers
authors.affiliation: Department of Computer Science, Boston University, 111 Cummington Street, Boston, MA, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xi
authors.affiliation: Tri-Institutional Training Program in Computational Biology and Medicine, 1300 York Avenue, Box 194, New York, NY, USA.|Division of Nutritional Sciences, Cornell University, Savage Hall, Ithaca, NY, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Locasale
authors.affiliation: Tri-Institutional Training Program in Computational Biology and Medicine, 1300 York Avenue, Box 194, New York, NY, USA.|Division of Nutritional Sciences, Cornell University, Savage Hall, Ithaca, NY, USA.
authors.forename: Zhenglong
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000465:Algorithms; D004798:Enzymes / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D064688:Metabolic Flux Analysis / Q000379:methods*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D012984:Software
chemical_list: D004798:Enzymes