Transporters will be depicted in the membrane in which they reside as blue lines whose arrowhead indicates the direction of transport. For gram-negative bacteria, periplasmic proteins will be depicted when identified in the PGDB. The Cellular Overview has been tested on Internet Explorer 8. It is recommended by the manufacturers Not to use Internet Explorer for the Cellular Overview process since its performance can be very poor.

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System-level visualization of metabolic networks -- Pathway Tools can automatically generate organism-specific metabolic charts that are called Cellular Overview diagrams as stated above Cellular Overview diagrams generated automatically -- Cellular Overview diagrams are generated automatically using an advanced layout algorithm. Following the first column can be any number of data columns. The user specifies whether the first column contains genes, metabolites, proteins, reactions or a mixture of types, and which subsequent data column or columns are to be used to generate the display—if multiple data columns are specified then an animated display is produced.

The user indicates whether the numbers represent relative or absolute measurements, whether they should be taken from a single column or as the ratio of two different columns and whether the values are based on a log or a linear scale. For microarray experiments, the desktop version of the Omics Viewer can also accept as input the output file generated by SAM [Significance Analysis of Microarrays 6 ], a plug-in for the Microsoft Excel spreadsheet program that combines the results of multiple repetitions of a single microarray experiment to produce lists of statistically significant positively and negatively regulated genes.

Most input files contain only a single type of data i. In this case, the metabolite profiling data would color the nodes in the diagram representing individual metabolites , and the gene expression data would be used to color the edges between the nodes representing reactions, enzymes and the genes that code for them.

When combining different types of data in this fashion, keep in mind the caveat that the scales for the two types of data must be the same in order for the results to be meaningful. This limitation can be avoided in the desktop version, where it is possible to overlay the data from multiple files, specifying a different color scheme for each to reflect differences in scale.

If a reaction has multiple isozymes, then multiple genes or proteins will be associated with a single reaction line, each with its own associated data value. However, on the full Cellular Overview Diagram there is room to draw only a single color for each line, so only one of the data values can be chosen for display we try to choose the value expected to be of most interest to users: the highest value for absolute measurements, or the one that shows the greatest deviation from 0 or 1 for relative measurements.

We have recently addressed this issue in the desktop Omics Viewer by allowing users to zero in on pathways of interest by navigating from the Omics Viewer to an individual pathway display, where they can see all their omics data superimposed on a much larger picture of that pathway. In this individual pathway display, multiple isozymes with different data values cause the reaction arrows to consist of multiple parallel lines, with one color for each isozyme.

When accessing the Omics Viewer over the web, we achieve the same effect, not by including omics data on regular pathway pages, but by showing it on magnified pathway images that pop up when the user clicks on a pathway in the cellular overview diagram—see Figure 3 for an example. The cellular overview diagram for E. Notice that in this magnified view, isozymes are distinguished as parallel lines within one reaction arrow, and gene names and their corresponding data values are drawn in the color for that data value.

The software can now also generate a table of magnified views of all pathways that have one or more experimental values exceeding a specified threshold, with omics data painted onto the pathway.

An example is shown in Figure 4. A portion of a table of E. The column on the right lists each enzyme in the pathway, its associated genes and, where available, its cellular location. The Pathway Tools' capabilities for overlaying multiple kinds of data onto both the overview as a whole and onto individual pathways, for showing time course data as an animation, and for allowing users to specify their own color schemes are intended to maximize the opportunities for scientists to derive biologically meaningful insights from their data.

Example uses of the Omics Viewer by life sciences researchers are as follows. The Conway laboratory investigated the relative significance of individual metabolic pathways for the colonization of Escherichia coli in the mouse intestine by analyzing time series and gene knockout gene expression data using the Omics Viewer 7. The Schoolnik laboratory investigated how the metabolism of Vibrio cholerae changes, and which metabolic pathways are selectively up- or down-regulated as the organism transitions from an aquatic environment to the mammalian gut, by analyzing gene expression experiments using the Omics Viewer.

Researchers at the Max Planck Institute of Molecular Plant Physiology used the Omics Viewer with a combination of gene expression and metabolite profiling data to identify and analyze changes in the metabolism of Arabidopsis thaliana under conditions of sulfur starvation 8.

The Supplementary Data attached to this study includes figures showing the overview diagram for Arabidopsis superimposed first with gene expression data and then with metabolite profiling data. The KEGG database 9 , to which the BioCyc databases are often compared, provides a single overview map for all organisms in KEGG, which contains links to functionally related groups of reference pathways. That diagram is not queryable or interactive in any other way, and there is no way to find out what individual nodes or lines represent other than by navigating to an individual reference pathway map.

Pathway Solutions, Inc. This tool does not offer animations or customized color schemes. Reactome 11 has produced an analog of our cellular overview diagram. Their diagram can be used for navigation and querying. It focuses primarily on human pathways, but can show subsets applicable to 14 additional eukaryotic model organisms. The Reactome SkyPainter tool maps omics data onto the reaction arrows in the overview diagram, including generating animations for time series data.

Because the Reactome overview contains only reaction arrows, and not individual metabolites, it is not suitable for displaying metabolomics data. It cannot show omics data on individual pathways, nor can it distinguish isozymes. Because all the overviews for the different model organisms are shown as subsets of the human overview, many pathways are missing from the overviews for other organisms. For example, although Reactome has an overview for A. Other available packages allow mapping of experimental data onto pathway images in various forms.

These packages show only single pathways their pathways are often defined somewhat differently , rather than a full cellular network. These examples attest to general recognition of the need for a biochemical overview map, but because the diagrams associated with these other tools are laid out by hand, their customizability is limited.

Our automated layout algorithms allow us to generate a customized overview diagram for each organism, and they can quickly regenerate the diagram when new pathways are added or spurious ones deleted. We are considering future extensions to our software to expand the abilities of users to visualize omics data in the context of cellular networks, including i extending the cellular overview to include representations of different types of gene products, such as transcriptional regulators, so that these genes and proteins can also be visualized using the Omics viewer; ii adding eukaryotic subcellular compartments to the overview; iii creating generic non-organism-specific overviews such as the one for bacteria, another for plants containing all the relevant MetaCyc pathways and iv adding further query operations, such as query by Gene Ontology ID.

The web version supports navigation and most of the Omics Viewer functionality, as indicated above. Accessing these features of the website requires a modern javascript-enabled web browser such as Firefox, Safari or Internet Explorer version 4. It is available free to academic or non-profit institutions for research use; a fee applies to other forms of use. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Read article at publisher's site DOI : Brief Bioinform , 22 3 , 01 May Metabolites , 11 2 , 22 Jan Metabolites , 10 5 , 15 May J Proteome Res , 18 11 , 14 Oct Nat Commun , 10 1 , 06 Sep To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

Latendresse M , Karp PD. BMC Bioinformatics , , 19 May Nucleic Acids Res , 36 database issue :D, 27 Oct Nucleic Acids Res , 38 database issue :D, 22 Oct Nucleic Acids Res , 44 d1 :D, 02 Nov Karp PD , Caspi R. Arch Toxicol , 85 9 , 27 Apr Review Free to read.

EcoSal Plus , 8 1 , 01 Nov Brief Bioinform , 22 1 , 01 Jan Contact us. Pathway Tools supports interrogation and exploration of cellular biochemical networks through the overview diagram. Furthermore, a software component called the Omics Viewer provides visual analysis of whole-organism datasets using the overview diagram as an organizing framework. Proteomics Data: Reaction lines and protein icons, where present are color-coded according to the concentration of the enzyme that catalyzes that reaction step.

Metabolomics Data: Compound icons are color-coded according to the concentration of the compound. Reaction Flux Data: Reaction lines are color-coded according to reaction flux values. Other Experimental Data: Any experiment, high-throughput or otherwise, in which data values are assigned to genes, proteins, reactions or metabolites can be viewed in a pathway context using the Omics Viewer.

Click here to go to the Webinar page, where you can watch the Comparative and Omics Tools in BioCyc instructional videos. More information about the Omics Viewer, including sample datafiles and displays. The Omics Viewer takes as input a tab-delimited data file that is stored on your local computer. The file contains relative or absolute data for a set of genes, proteins, reactions, metabolites, or some combination.