Analysis of biochemical reaction graph application to heterotrophic plant cell metabolism

Dedication

Acknowledgements

Abstract

Résumé

Table of Contents

Introduction

Metabolic Networks and Their Specifications

Context
Metabolism
- Molecules
- Processes
Basic concepts in Metabolic Pathways Analysis
- Metabolic Pathways and Networks
- Metabolic networks features
Computational Models of Metabolism
- A classical model: Kinetic Modelling
- Constraint-Based Models
- Conventional Functional Models
- Graph-Based Models
Approaches of Metabolic Networks Analysis
- Stoichiometric Analysis
- Flux Balance Analysis
- Petri net
- Elementary Flux Modes Analysis
Description of our experimental data
Summary

Network-Based Analysis of Biological Graph

Generalities of graphs
- Definitions
- Global structural properties
- Computing global structural properties of concrete networks
- Checking network modularity
Complex networks
- Small-world networks
- Scale-free networks
- Metabolism as a complex network
- Complex networks analysis
- Experiments: Finding high-centrality hubs
- Community detection and Subgraph extraction
Conclusion

Computing Minimal Cut Sets

Minimum cuts in graph
- Concepts of s-t cut
- Minimum cuts algorithms
Minimal Cut Sets in Metabolic Networks
- Introduction
- Defining minimal cut sets of a metabolic network
- Determining MCSs
- Improvements of MCS concepts
- Methods to improve MCSs computing
- Computing tools
Experiments
- Contrast in EFMs and MCSs results
Collaboration between EFMs and MCSs analysis
- Stating the principal idea
- Stopping the production of external citrate in Krebs cycle
Conclusion

Application to Heterotrophic Plant Cell Networks

Metabolic Network of Heterotrophic Plant Cells
- Description of the first version of the network
- Description of the redefined network
- Computation of global structural properties
- Computation of Elementary Flux Modes
- Computation of Minimal Cut Sets
Analysis of specific metabolic productions
- The reason of choosing five cases
- Presentation of the five sub networks
Effects of stopping the entrance of glucose
- Connectivity of the sub networks
- Reaction hubs and metabolite hubs
- The occurrences of reactions and the length of EFMs
- Combining MCSs result and EFMs analysis
- Motif branches into MNHPC
Conclusion and Future works

Conclusion

Bibliography

Index

Acronyms

List of Abbreviations

List of Figures

List of Tables

Appendix

Data Descriptions

Implementation

Methods and models from Graph Theory

Hypergraphs
Petri Net
- Simple Networks
- Random Networks
Minimum cut algorithms in Graph Theory
- Flow-based approaches
- Contraction Based Approaches
- How to find all minimum cuts
Applications of MCSs
- Evaluation of system reliability
- Fault Trees
- The k-cut problem
- Image Segmentation of Computer Vision

Other results

Genes rules defined in regEfmtool
Drawings corresponding the sub networks without the unused reactions
- Vac_f, Vac_g and Vac_s in the Vacuole compartment
- Vgl_out in the Cytosol compartment
- Vss in the Plastid compartment
List of all different motifs

Extending works

Finding the isolated reactions
Finding the longest chain of reactions
Clustering the reactions into groups
- Finding motifs
- Analysis of Minimal Cut Sets

Scientific Activities