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Figure 1.

Web interface and workflow of CINPER.

(A) a schematic diagram of workflow of CINPER, showing the four-step process of gene-network reconstruction: (1) collection of template networks, (2) construction of initial target network, (3) expansion of initial target network, and (4) validation of the prediction network; (B) a list of all the genes or interactions (not shown) in the target pathway in a sortable and editable table, and (C) a display of the current pathway model shown in a clickable graphics viewer, where each red rectangle represents a gene in the initial pathway model created through orthologous gene mapping from a template pathway; each cyan rectangle represents a gene predicted to be involved in the target pathway based on functional relations with genes in the initial pathway model; and the color of an edge represents the type of a functional relation between two involved genes.

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Table 1.

17 predicted pathways from E. coli to B. subtilis by CINPER based on MetaCyc.

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Figure 2.

A screenshot of iron homeostasis network in Synechocystis PCC6803 predicted by CINPER.

The window of network visualization consists of three parts: the left part is a zoomable graphic display, in which a small operation panel in the middle right side can zoom in or out the display; the right upper part is the information for the selected gene in the left graphic display, such as the gene symbol, GI number and gene function; and the right bottom part is a legend to define the meanings of the shapes in the left part: round rectangles are predicted genes, among which red ones are genes in the initial network and the cyan ones are genes recruited through functional relationship; triangles are validated genes using gene expression data; color-coded arrows between two genes represent different interaction types, red for genes in the same pathway, green for genes in the same operon, blue for genes in the same regulon and black for genes with functional relationships as defined by the STRING database, such as protein-protein physical interaction, similar phylogenetic profile or expression profile.

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Figure 3.

A schematic diagram of iron homeostasis network in Synechocystis PCC6803, drawn using the PathVisio program [40], showing that iron homeostasis is regulated by the global regulator Fur: when the cell is replete with iron, its bounded form (Fe-Fur) represses the transcription of iron transporters; and when the cell is low in iron, its iron-free form (apo-Fur) activates iron transporters and repress the transcription of iron storage and utilization proteins to increase the intracellular iron.

Proteins are represented as ellipses, and genes are rectangles; arrows are activation processes, and T-bars are repression processes; and dashed lines indicate indirect or hypothetical processes.

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