title: Diagnostics for stochastic genome-scale modeling via model slicing and debugging.
abstract: Modeling of biological behavior has evolved from simple gene expression plots represented by mathematical equations to genome-scale systems biology networks. However, due to obstacles in complexity and scalability of creating genome-scale models, several biological modelers have turned to programming or scripting languages and away from modeling fundamentals. In doing so, they have traded the ability to have exchangeable, standardized model representation formats, while those that remain true to standardized model representation are faced with challenges in model complexity and analysis. We have developed a model diagnostic methodology inspired by program slicing and debugging and demonstrate the effectiveness of the methodology on a genome-scale metabolic network model published in the BioModels database. The computer-aided identification revealed specific points of interest such as reversibility of reactions, initialization of species amounts, and parameter estimation that improved a candidate cell's adenosine triphosphate production. We then compared the advantages of our methodology over other modeling techniques such as model checking and model reduction. A software application that implements the methodology is available at http://gel.ym.edu.tw/gcs/.
authors.affiliation: Bioinformatics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, Taiwan; Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan; Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chuan-Hsiung
authors.initials: CH
authors.lastname: Chang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000465:Algorithms; D004926:Escherichia coli / Q000378:metabolism; D020407:Internet; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D012984:Software; D049490:Systems Biology; D014584:User-Computer Interface
chemical_list: D000255:Adenosine Triphosphate