3. Uematsu S, Akira S (2007) Toll-like receptors and Type I interferons. J Biol Chem 282: 15319–15323. 4. Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2: 675–680. 5. Finlay BB, McFadden G (2006) Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 124: 767–782. 6. O’Neill LA (2006) Targeting signal transduction as a strategy to treat inflammatory diseases. Nat Rev Drug Discov 5: 549–563. 7. Pries R, Wulff S, Wollenberg B (2008) Toll-like receptor modulation in head and neck cancer. Crit Rev Immunol 28: 201–213. 8. Cook DN, Pisetsky DS, Schwartz DA (2004) Toll-like receptors in the pathogenesis of human disease. Nat Immunol 10: 975–979. 9. Aderem A (2005) Systems biology: its practice and challenges. Cell 121: 511–513. 10. Hirotani T, Yamamoto M, Kumagai Y, Uematsu S, Kawase I, et al. (2005) Regulation of lipopolysaccharide-inducible genes by MyD88 and Toll/IL-1 domain containing adaptor inducing IFN-beta. Biochem Biophys Res Commun 328: 383–392. 11. Krishnan J, Selvarajoo K, Tsuchiya M, Lee G, Choi S (2007) Toll-like receptor signal transduction. Exp Mol Med 39: 421–438. 12. Nilsson R, Bajic VB, Suzuki H, di Bernardo D, Bjo¨rkegren J, et al. (2006) Transcriptional network dynamics in macrophage activation. Genomics 88: 133–142. 13. Karsenti E (2008) Self-organization in cell biology: a brief history. Nat Rev Mol Cell Biol 9: 255–262. 14. Baraba´si AL, Oltvai ZN (2004) Network Biology: Understanding the cell’s functional organization. Nat Rev Genet 5: 101–113. 15. Kurakin A (2005) Self-organization vs Watchmaker: stochastic gene expression and cell differentiation. Dev Genes Evol 215: 46–52. 16. Huang S, Eichler G, Bar-Yan Y, Ingber DE (2005) Cell Fates as High- Dimensional Attractor States of a Complex Gene Regulatory Networks. Phys Rev Lett 94: 12870–12874. 17. Farkas I, Jeong H, Vicsek T, Barabasi AL, Oltvai ZN (2003) The topology of the transcription regulatory network in the yeast, Saccharomyces cerevisiae. Physica A 318: 601–612. 18. Klebanov L, Yakovlev A (2007) How high is the level of technical noise in microarray data? Biol Direct 2: 9. 19. Shi L, Reid LH, Jones WD, Shippy R, Warrington JA, et al. (2006) The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements. Nat Biotech 24: 1151–1161. 20. Chang H, Hemberg M, Barahona M, Ingber DE, Huang S (2008) Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature 453: 544–548. 21. Kawai T, Adachi O, Ogawa T, Takeda K, Akira S (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11: 115–122. 22. Dahlquist KD, Salomonis N, Vranizan K, Lawlor SC, Conklin BR (2002) GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat Genet 31: 19–20. 23. Bjo¨rkbacka H, Fitzgerald KA, Huet F, Li X, Gregory JA, et al. (2004) The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol Genomics 19: 319–330. Macrophage Genome-Wide Control 24. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, et al. (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301: 640–643. 25. Ouyang X, Negishi H, Takeda R, Fujita Y, Taniguchi T, et al. (2007) Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation. Biochem Biophys Res Commun 354: 1045–1051. 26. Selvarajoo K (2008) Decoding the Signaling Mechanism of Toll-Like Receptor 4 Pathways in Wild Type and Knockouts. In: Ghosh S, Arjunan S, Dhar P, Tomita M, eds. E-Cell System—Basic Concepts and Applications. New York: Landes Bioscience and Springer Science+Business Media, In press. 27. Tsuchiya M, Selvarajoo K, Piras V, Tomita M, Giuliani A (2008) Local and Global responses in complex gene regulation networks. Physica A 388: 1738–1746. 28. Sherman BT, Huang da W, Tan Q, Guo Y, Bour S, et al. (2007) DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics 8: 426. 29. Selvarajoo K, Takada Y, Gohda J, Helmy M, Akira S (2008) Signaling flux redistribution at toll-like receptor pathway junctions. PLoS ONE 3: e3430. 30. Klevecz R, Li C, Marcus I, Frankel P (2008) Collective behavior in gene regulation: The cell is an oscillator, the cell cycle a developmental process. FEBS J 275: 2372–2384. 31. Tsuchiya M, Wong ST, Yeo ZX, Colosimo A, Palumbo MC, et al. (2007) Gene expression waves: cell cycle independent collective dynamics in cultured cells. FEBS J 274: 2874–2886. 32. Elowitz MB, Levine AJ, Siggia ED, Swain PS (2002) Stochastic gene expression in a single cell.Science. Science 297: 1129–1131. 33. Dunlop MJ, Cox RS 3rd, Levine JH, Murray RM, Elowitz MB (2008) Regulatory activity revealed by dynamic correlations in gene expression noise. Nat Genet 40: 1493–1498. 34. Cohen AA, Geva-Zatorsky N, Eden E, Frenkel-Morgenstern M, Issaeva I, et al. (2008) Dynamic proteomics of individual cancer cells in response to drugs. Science 321: 1511–1516. 35. Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185–193. 36. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, et al. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249–264. 37. McClintick JN, Edenberg HJ (2006) Effects of filtering by Present call on analysis of microarray experiments. BMC bioinformatics 7: 49. 38. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, et al. (2000) Gene Ontology: tool for the unification of biology. Nat Genet 25: 25–29. 39. Thomas PD, Campbell MJ, Kejariwal A, Mi H, Karlak B, et al. (2003) PANTHER: a library of protein families and subfamilies indexed by function. Genome Res 13: 2129–2141. 40. Kanehisa M, Goto S (2000) KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 28: 27–30. PLoS ONE | www.plosone.org 13 March 2009 | Volume 4 | Issue 3 | e4905