A systems approach to identifying correlated gene targets for the loss of colour pigmentation in plants

Clark, Sangaalofa Tooki; Verwoerd, W.S.

doi:10.1186/1471-2105-12-343

Cited by 42 publications

(39 citation statements)

References 56 publications

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“…Another study explored properties of the network of flavonoid biosynthesis taken from the KEGG database [18]. A large data-based network has also been constructed for anthocyanin biosynthesis in Arabidopsis thaliana [19]. This network was used to search for the minimal set of metabolites and enzymes that lead to anthocyanin production.…”

Section: Introductionmentioning

confidence: 99%

The Flavonoid Pathway in Tomato Seedlings: Transcript Abundance and the Modeling of Metabolite Dynamics

et al. 2013

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Flavonoids are secondary metabolites present in all terrestrial plants. The flavonoid pathway has been extensively studied, and many of the involved genes and metabolites have been described in the literature. Despite this extensive knowledge, the functioning of the pathway in vivo is still poorly understood. Here, we study the flavonoid pathway using both experiments and mathematical models. We measured flavonoid metabolite dynamics in two tissues, hypocotyls and cotyledons, during tomato seedling development. Interestingly, the same backbone of interactions leads to very different accumulation patterns in the different tissues. Initially, we developed a mathematical model with constant enzyme concentrations that described the metabolic networks separately in both tissues. This model was unable to fit the measured flavonoid dynamics in the hypocotyls, even if we allowed unrealistic parameter values. This suggested us to investigate the effect of transcript abundance on flavonoid accumulation. We found that the expression of candidate flavonoid genes varies considerably with time. Variation in transcript abundance results in enzymatic variation, which could have a large effect on metabolite accumulation. Candidate transcript abundance was included in the mathematical model as representative for enzyme concentration. We fitted the resulting model to the flavonoid dynamics in the cotyledons, and tested it by applying it to the data from hypocotyls. When transcript abundance is included, we are indeed able to explain flavonoid dynamics in both tissues. Importantly, this is possible under the biologically relevant restriction that the enzymatic properties estimated by the model are conserved between the tissues.

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Section: Introductionmentioning

confidence: 99%

The Flavonoid Pathway in Tomato Seedlings: Transcript Abundance and the Modeling of Metabolite Dynamics

et al. 2013

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“…The product vector compiled for an Arabidopsis flower using FlavNet [18] and information from [17] is shown in Table 5 where a one (1) represents the presence, and a zero (0) the absence, of the compound in the flower: …”

Section: Resultsmentioning

confidence: 99%

“…Information from [17] was used in conjunction with the flavonoid subnetwork, FlavNet, used in [18], to compile a product binary vector for an Arabidopsis flower, specifying which flavonoids are present and which are not.…”

Section: Methods Of Applicationmentioning

confidence: 99%

“…Looking at their position in the network, the reactions originate from the external trans-cinnamate substrate (refer to Figure 1 and Figure 3 of [18]) and lead to the formation of kaempferol and quercetin compounds and their derivatives as well as anthocyanin compounds although not the anthocyanin derivatives. If the yellow part containing the 20 reactions in the above Table 6 is taken out, the remaining matrix is as shown in Figure 6 with the reactions on the vertical axis and the viable EMs on the horizontal axis.…”

Section: Analysing the Expression Matrix Xmentioning

confidence: 99%

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A Systems Approach for Determining Gene Expression from Experimental Observation of Compound Presence and Absence

Clark¹,

Verwoerd²

2014

ABB

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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-Phenyla-lanine, 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.

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“…For example, we have used MCSs [16] to study the functionalities of anthocyanin related genes in flowering plants.…”

Section: Defining Minimal Cut Setsmentioning

confidence: 99%

Minimal Cut Sets and the Use of Failure Modes in Metabolic Networks

Clark

Verwoerd

2012

Metabolites

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A minimal cut set is a minimal set of reactions whose inactivation would guarantee a failure in a certain network function or functions. Minimal cut sets (MCSs) were initially developed from the metabolic pathway analysis method (MPA) of elementary modes (EMs); they provide a way of identifying target genes for eliminating a certain objective function from a holistic perspective that takes into account the structure of the whole metabolic network. The concept of MCSs is fairly new and still being explored and developed; the initial concept has developed into a generalized form and its similarity to other network characterizations are discussed. MCSs can be used in conjunction with other constraints-based methods to get a better understanding of the capability of metabolic networks and the interrelationship between metabolites and enzymes/genes. The concept could play an important role in systems biology by contributing to fields such as metabolic and genetic engineering where it could assist in finding ways of producing industrially relevant compounds from renewable resources, not only for economical, but also for sustainability, reasons.

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A systems approach to identifying correlated gene targets for the loss of colour pigmentation in plants

Cited by 42 publications

References 56 publications

The Flavonoid Pathway in Tomato Seedlings: Transcript Abundance and the Modeling of Metabolite Dynamics

The Flavonoid Pathway in Tomato Seedlings: Transcript Abundance and the Modeling of Metabolite Dynamics

A Systems Approach for Determining Gene Expression from Experimental Observation of Compound Presence and Absence

Minimal Cut Sets and the Use of Failure Modes in Metabolic Networks

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