Abstract
Different genes are expressed in different tissues, depending on functional objectives and selection pressures. Based on complete knowledge of the structure of the metabolic network and all the reactions taking place in the cell, elementary modes (EMs) and minimal cut sets (MCSs) can relate compounds observed in a tissue, to the genes being expressed by respectively providing the full set of non-decomposable routes of reactions and compounds that lead to the synthesis of external products, and the full set of possible target genes for blocking the synthesis of external products. So, for a particular tissue, only the EMs containing the reactions that are related to the genes being expressed in those tissues, are active for the production of the corresponding compounds. This concept is used to develop an algorithm for determining a matrix of reactions (which can be related to corresponding genes) taking place in a tissue, using experimental observations of compounds in a tissue. The program is applied to the Arabidopsis flower and identified 20 core reactions occurring in all the viable EMs. They originate from the trans-cinnamate compound and lead to the formation of kaempferol and quercetin compounds and their derivatives, as well as anthocyanin compounds. Analyses of the patterns in the matrix identify reaction sets related to certain functions such as the formation of derivatives of the two anthocyanin compounds present, as well as the reactions leading from the network’s external substrate erythrose-4P to L-Phenylalanine, cinnamyl-alc to trans-cinnamate and so on. The program can be used to successfully determine genes taking place in a tissue, and the patterns in the resulting matrix can be analysed to determine gene sets and the state of the tissue.
Highlights
The metabolic pathway analysis concepts of elementary modes (EMs) and minimal cut sets (MCSs) represent the core concepts used in developing the method presented here
For a particular tissue, only the EMs containing the reactions that are related to the genes being expressed in those tissues, are active to produce the corresponding compounds
Each EM forms a route consisting of a non-reducible set of reactions that lead to the formation of the compound so, in effect, form a candidate expression vector for the compound present in the tissue
Summary
The metabolic pathway analysis concepts of elementary modes (EMs) and minimal cut sets (MCSs) represent the core concepts used in developing the method presented here. Minimal cut sets are complementary to EMs, and consist of the minimal sets of reactions that, when blocked, will repress a certain metabolic functionality by preventing the network from achieving steady state. The metabolic network contains all gene-related reactions and metabolites for that organism, in real life only certain genes or enzymes are expressed in certain tissues. For a particular tissue, only the EMs containing the reactions that are related to the genes being expressed in those tissues, are active to produce the corresponding compounds. Would have the same EMs [4] and MCSs [5] It is just a matter of determining which of these are activated for a certain cell in relation to the genes or enzymes that are expressed or suppressed
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