Metabolic pathways visualization

A directed graph search is available where compounds are nodes and metabolic steps are edges. The server finds the shortest allowable path between one node and another. One can limit the search to steps that occur in a certain kingdom and can also choose to display only pathways visually connected on the metabolic pathway chart. There are thousands of connections that are not drawn on the chart but can be found by using this search. 

The MetaCyc database is the result of a collaborative effort between SRI International (see the website and useful links on this document), the Carnegie Institution, and Stanford University in creating a comprehensive database collected from literature and cyber sources. The MetaCyc database contains metabolic pathways (with citations), reactions, enzymes, and substrates. This database does not offer genomic data, but it does supply its own software and visualization tools (297). 

E. coli. EcoCyc allows for visualizing of genes on chromosomes, a biochemical reaction, or pathway. EcoCyc also allows for computational investigations of the metabolism, design, evaluation, and simulation of metabolic pathways (298). 

The ExPASy server (www.expasy.chl is one of the most useful servers, where almost any bioinforma tic tool can be found, together with useful links to other websites such as NCBI or EBI. The several access databases are descriptive, easy to follow, and up to date. Protein data bank searches with SwissProt or Trembl, as well as sequence alignments using either SimAlign (for two sequences) or ClustalW (for more than two protein sequences) can be started from ExPASy, to name just a few of the possibilities available. Access is also given to the Roche Applied Science Biochemical pathways where either keyword searches for particular enzymes or for metabolites can be performed, or entire metabolic pathways or sections thereof can be visualized. Proteomics evaluation is also available on ExPASy, which features free 2D-PAGE software called Melanie. 

We focus on the combination of transcriptomics and metabolomics and more specifically on microarray data, which is currently the most used method for gene expression profiling and is used on a routine basis. In the first paragraphs, we briefly revise the extraction of mRNA or metabolites, their measurement, quality control of data, and analysis methods. Afterward two different types of data fusion and recent tools and publications are reviewed, followed by visualization methods for obtained data. Lastly, the metabolite annotation Web server MassTRIX is presented. This Web server allows combined analysis of transcriptomic and metabolomic data in the context of metabolic pathways. We compared the metabolomics part against similar tools and give a short outlook on the next version of MassTRIX, MassTRIX 4. 

After identification of gene-metabolite associations or enrichment analysis, visualization is a second key point. Results from low-level data fusion often yields pairwise correlations, which can be visualized using networks. In the case of high-level data fusion, a combined visualization is used on metabolic pathways (e.g., the well-known pathway maps from KEGG are preferred). We discuss some technical resources for both visualization types. However, much more tools for different kinds of visualization exist and are reviewed elsewhere (29). 

The main functionality of MassTRIX is the direct annotation of mass spectro-metric data to putative metabolites and direct mapping of these results to metabolic pathways. For more complex data visualization in networks, we recommend using MassTRIX annotation together with raw data in VANTED. 

Pathway Editor is a tool to visualize a sequence of structures in a multistep reaction or a metabolic pathway. 

Pathway Articulator or PathArt (table 7.1) is built around a database of signaling and metabolic pathways derived from manual curation of the literature. Database elements are annotated with links to several vocabularies (GO, Locuslink, CAS, etc.), and displayed in an editable pathway visualizer. 

MIBG I-MIBG was also used to image adrenal medulla and its neoplasms. It follows the same metabolic pathways as catecholamines, in particular that of norepinephrine, and is stored in surrenal cells cytoplasm. It enables the visualization of many neuroendocrine tumors that fix... 

Figure 2A is an example of a very simple metabolic pathway in which the starting state is vertex 1. This state can be considered to be the dietary nutrient. If states 4 and 5 are termination states, the pathway can be represented as the closed diagram of Fig. 2B. There are two cycles in Fig. 2B one of which can be visualized as giving rise to the observed response. The expression derived for the probability of completion of either cycle is a 1 1...

The object of metabolic control theory is to provide a sound mathematical foundation for the quantitative estimation of the role played by individual enzymes on the control of flux through a metabolic pathway and also the control exerted by individual enzymes on the concentration of intermediate metabolites in the pathway. The general principles of metabolic control theory and biochemical systems theory can be visualized by considering the simple metabolic pathway in Fig. 6. The numbers above the arrows... 

CathaCyc presents a variety of tools for the visualization and analysis of metabolic networks and omics data [61] and will certainly help in discovering missing enzymes, studying metabolic pathway evolution, and, ultimately, improving... 

Fig. 5. Gene Regulatory Network constructed using Cytoscape for visualizing the interconnection of the Lipid Metabolic Pathways restricted to L. major. ...

Upon presenting the Nobel Prize to Karrer, Wilhelm Palmaer, chair of the prize committee at the time, described him as a scientist with the ability to visualize great and important problems as well as their smaller parts and one who in his own unique way approached problems and pursued new ideas by using his own methods [61] . Karrer s methodology has borne much fruit over the decades. The spinoffs from his work on the carotenoids and xanthophylls is still evolving today intense research on vision, vitamins, hormones, metabolic pathways, and enzymes. 

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