Flux-dependent graphs for metabolic networks
Cells adapt their metabolic fluxes in response to changes in the environment. We present a framework for the systematic construction of flux-based graphs derived from organism-wide metabolic networks. Our graphs encode the directionality of metabolic fluxes via edges that represent the flow of metabolites from source to target reactions. The methodology can be applied in the absence of a specific biological context by modelling fluxes probabilistically, or can be tailored to different environmental conditions by incorporating flux distributions computed through constraint-based approaches such as Flux Balance Analysis. We illustrate our approach on the central carbon metabolism of Escherichia coli and on a metabolic model of human hepatocytes. The flux-dependent graphs under various environmental conditions and genetic perturbations exhibit systemic changes in their topological and community structure, which capture the re-routing of metabolic fluxes and the varying importance of specific reactions and pathways. By integrating constraint-based models and tools from network science, our framework allows the study of context-specific metabolic responses at a system level beyond standard pathway descriptions.
Code (0)
등록된 구현이 없습니다.
Similar Papers 제목 키워드 기반
Metabolic graphs, LIFE method and the modeling of drug action on Mycobacterium tuberculosis
This paper serves as a framework for designing advanced models for drug action on metabolism. Drug treatment may affect metabolism by either enhancing or inhibiting metabolic reactions comprising a metabolic network. We …
Bayesian Metabolic Flux Analysis reveals intracellular flux couplings
Metabolic flux balance analyses are a standard tool in analysing metabolic reaction rates compatible with measurements, steady-state and the metabolic reaction network stoichiometry. Flux analysis methods commonly place …
Structural thermokinetic modelling
Translating metabolic networks into dynamic models is difficult if kinetic constants are unknown. Structural Kinetic Modelling (SKM) replaces reaction elasticities by independent random numbers. Here I propose a variant …
Enzyme economy and metabolic control
The metabolic state of a cell, comprising fluxes, metabolite concentrations and enzyme levels, is shaped by a compromise between metabolic benefit and enzyme cost. This hypothesis and its consequences can be studied by c…
Hybrid physics-informed metabolic cybergenetics: process rates augmented with machine-learning surrogates informed by flux balance analysis
Metabolic cybergenetics is a promising concept that interfaces gene expression and cellular metabolism with computers for real-time dynamic metabolic control. The focus is on control at the transcriptional level, serving…