TY  - JOUR
A1  - Frioux, Clémence
A1  - Schaub, Torsten H.
A1  - Schellhorn, Sebastian
A1  - Siegel, Anne
A1  - Wanko, Philipp
T1  - Hybrid metabolic network completion
JF  - Theory and practice of logic programming
N2  - Metabolic networks play a crucial role in biology since they capture all chemical reactions in an organism. While there are networks of high quality for many model organisms, networks for less studied organisms are often of poor quality and suffer from incompleteness. To this end, we introduced in previous work an answer set programming (ASP)-based approach to metabolic network completion. Although this qualitative approach allows for restoring moderately degraded networks, it fails to restore highly degraded ones. This is because it ignores quantitative constraints capturing reaction rates. To address this problem, we propose a hybrid approach to metabolic network completion that integrates our qualitative ASP approach with quantitative means for capturing reaction rates. We begin by formally reconciling existing stoichiometric and topological approaches to network completion in a unified formalism. With it, we develop a hybrid ASP encoding and rely upon the theory reasoning capacities of the ASP system dingo for solving the resulting logic program with linear constraints over reals. We empirically evaluate our approach by means of the metabolic network of Escherichia coli. Our analysis shows that our novel approach yields greatly superior results than obtainable from purely qualitative or quantitative approaches.
KW  - answer set programming
KW  - metabolic network
KW  - gap-filling
KW  - linear programming
KW  - hybrid solving
KW  - bioinformatics
Y1  - 2018
U6  - https://doi.org/10.1017/S1471068418000455
SN  - 1471-0684
SN  - 1475-3081
VL  - 19
IS  - 1
SP  - 83
EP  - 108
PB  - Cambridge University Press
CY  - New York
ER  - 
TY  - JOUR
A1  - Küken, Anika
A1  - Gennermann, Kristin
A1  - Nikoloski, Zoran
T1  - Characterization of maximal enzyme catalytic rates in central metabolism of Arabidopsis thaliana
JF  - The plant journal
N2  - Availability of plant-specific enzyme kinetic data is scarce, limiting the predictive power of metabolic models and precluding identification of genetic factors of enzyme properties. Enzyme kinetic data are measuredin vitro, often under non-physiological conditions, and conclusions elicited from modeling warrant caution. Here we estimate maximalin vivocatalytic rates for 168 plant enzymes, including photosystems I and II, cytochrome-b6f complex, ATP-citrate synthase, sucrose-phosphate synthase as well as enzymes from amino acid synthesis with previously undocumented enzyme kinetic data in BRENDA. The estimations are obtained by integrating condition-specific quantitative proteomics data, maximal rates of selected enzymes, growth measurements fromArabidopsis thalianarosette with and fluxes through canonical pathways in a constraint-based model of leaf metabolism. In comparison to findings inEscherichia coli, we demonstrate weaker concordance between the plant-specificin vitroandin vivoenzyme catalytic rates due to a low degree of enzyme saturation. This is supported by the finding that concentrations of nicotinamide adenine dinucleotide (phosphate), adenosine triphosphate and uridine triphosphate, calculated based on our maximalin vivocatalytic rates, and available quantitative metabolomics data are below reportedKMvalues and, therefore, indicate undersaturation of respective enzymes. Our findings show that genome-wide profiling of enzyme kinetic properties is feasible in plants, paving the way for understanding resource allocation.
KW  - Arabidopsis thaliana
KW  - constraint-based modeling
KW  - enzyme catalytic rates
KW  - kinetic parameter
KW  - metabolic network
KW  - turnover number
Y1  - 2020
U6  - https://doi.org/10.1111/tpj.14890
SN  - 0960-7412
SN  - 1365-313X
VL  - 103
IS  - 6
SP  - 2168
EP  - 2177
PB  - Wiley
CY  - Oxford
ER  -