الفهرس 
DEDICATION
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Abstract
Systems biology is a branch in life science. It aims to integrate the experimental results, from bacterial and fungal fermentation, biochemistry, biophysics, genomics and molecular biology, into mathematical models. It uses those models to represent, simulate and predict what happen in the organism. The main aim of systems biology is to represent the organism into the computer, by collection all known information about this organism in a network form. This organism is called in silico organism which has a lot of applications:
Synthetic biology for biosynthesis the biofuel and pharm compounds in the model organisms such as yeast and E. Coli;
Metabolic engineering for optimization production of those products;
Systems medicine for modeling gut microbiota and cancer growth.
This thesis aims to study genome-scale metabolic models. They contain the known chemical reaction occurring inside the cell or tissue, where each reaction is assigned with gene(s).
The thesis has five chapters:
Chapter 1 is an introduction to systems biology. We describe how the in silico organism represented in to the computer through three main biological networks: metabolic, signal transduction and
V
regulatory transcription network (see figure 1.1). In addition, we mention how to reconstruct those networks using two methods:
up-down method uses the omics methods such as transcriptomics, metabolomics and proteomics (see Figure 1.2);
Bottom-up method which builds the draft model from bioinformatics databases and literature. This darft model will curate manually to fill the gaps in the model (see figure 1.3).
Systems biology integrates between the up-down and bottom-up methods, in order to look to the model with holistic view. The integration is repeated many times until the good model w.