Research
A functional map of NFκB signaling identifies novel modulators and multiple system controls
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* Corresponding author: Russell S Thomas rthomas@thehamner.org
1 The Hamner Institutes for Health Sciences, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA
2 Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, CA 92121, USA
3 Institute for Translational Medicine and Therapeutics, 810 Biomedical Research Building, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA
4 Almac Diagnostics, 801-1 Capitola Drive, Durham, NC 27713, USA
Genome Biology 2007, 8:R104 doi:10.1186/gb-2007-8-6-r104
Published: 6 June 2007Additional files
Additional data file 1:
A complete list of positive NFκB modulators identified using the gain-of-function full-length gene screens.
Format: XLS Size: 45KB Download file
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Additional data file 2:
A complete list of negative NFκB modulators identified using the loss-of-function full-length gene screens.
Format: XLS Size: 38KB Download file
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Additional data file 3:
A table listing the reduction in NFκB activation by the positive modulators using the IKBKB, IKBKG, MAP3K7, and TRAF2 dominant-negative mutants.
Format: XLS Size: 101KB Download file
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Additional data file 4:
A table listing the reduction in NFκB activation by a constitutively active IKBKB mutant using the negative NFκB modulators.
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Additional data file 5:
A figure of the overlap and location of positive and negative modulators identified in the cell-based screens within the canonical TNF (A) and IL1 (B) signaling pathways. The signaling pathways were obtained from the Human Protein Reference Database and visualized using GenMAPP 2.1. The green shaded boxes represent positive modulators and red shaded boxes represent negative modulators. Green shaded boxes with red borders represent modulators that were identified as both positive and negative.
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Additional data file 6:
A figure showing the overlap and location of positive and negative modulators identified in the cell-based screens within the canonical B-cell receptor (A) and T-cell receptor (B) signaling pathways. The signaling pathways were obtained from the Human Protein Reference Database and visualized using GenMAPP 2.1. The green shaded boxes represent positive modulators and red shaded boxes represent negative modulators. Green shaded boxes with red borders represent modulators that were identified as both positive and negative.
Format: JPEG Size: 3.4MB Download file
Additional data file 7:
A figure showing a network map of the NFκB modulators. An adjacency matrix was constructed on the basis of the orientation flags from the dominant-negative and constitutively active screens (that is, upstream, downstream, or unclassified). The adjacency matrix containing the experimental data was merged with a separate adjacency matrix containing members of the currently accepted NFκB signaling network. Based on the combined adjacency matrix, a network map was constructed as a rooted tree with the NFκB complex serving as the obligate root node. The longest path was calculated from each terminal node to the root node. Peach nodes = positive modulators; green nodes = negative modulators; pink nodes = genes identified as both positive and negative modulators; orange nodes = members of the known NFκB signaling network; red nodes = dominant-negative mutants (plus TRAF2); blue nodes = positive modulators whose network location was adjusted based on the currently accepted NFκB network structure.
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