title: Context-Specific Metabolic Model Extraction Based on Regularized Least Squares Optimization.
abstract: Genome-scale metabolic models have proven highly valuable in investigating cell physiology. Recent advances include the development of methods to extract context-specific models capable of describing metabolism under more specific scenarios (e.g., cell types). Yet, none of the existing computational approaches allows for a fully automated model extraction and determination of a flux distribution independent of user-defined parameters. Here we present RegrEx, a fully automated approach that relies solely on context-specific data and ℓ1-norm regularization to extract a context-specific model and to provide a flux distribution that maximizes its correlation to data. Moreover, the publically available implementation of RegrEx was used to extract 11 context-specific human models using publicly available RNAseq expression profiles, Recon1 and also Recon2, the most recent human metabolic model. The comparison of the performance of RegrEx and its contending alternatives demonstrates that the proposed method extracts models for which both the structure, i.e., reactions included, and the flux distributions are in concordance with the employed data. These findings are supported by validation and comparison of method performance on additional data not used in context-specific model extraction. Therefore, our study sets the ground for applications of other regularization techniques in large-scale metabolic modeling.
authors.affiliation: Systems Biology and Mathematical Modeling Group, Max Planck Institute of Molecular Plant Physiology (MPIMP), Potsdam-Golm, Germany.
authors.forename: Semidán
authors.initials: S
authors.lastname: Robaina Estévez
authors.affiliation: Systems Biology and Mathematical Modeling Group, Max Planck Institute of Molecular Plant Physiology (MPIMP), Potsdam-Golm, Germany.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Nikoloski
mesh_terms: D006801:Humans; D016018:Least-Squares Analysis; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D017423:Sequence Analysis, RNA; D059467:Transcriptome