title: Information transduction capacity of noisy biochemical signaling networks.
abstract: Molecular noise restricts the ability of an individual cell to resolve input signals of different strengths and gather information about the external environment. Transmitting information through complex signaling networks with redundancies can overcome this limitation. We developed an integrative theoretical and experimental framework, based on the formalism of information theory, to quantitatively predict and measure the amount of information transduced by molecular and cellular networks. Analyzing tumor necrosis factor (TNF) signaling revealed that individual TNF signaling pathways transduce information sufficient for accurate binary decisions, and an upstream bottleneck limits the information gained via multiple integrated pathways. Negative feedback to this bottleneck could both alleviate and enhance its limiting effect, despite decreasing noise. Bottlenecks likewise constrain information attained by networks signaling through multiple genes or cells.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Cheong
authors.forename: Alex
authors.initials: A
authors.lastname: Rhee
authors.forename: Chiaochun Joanne
authors.initials: CJ
authors.lastname: Wang
authors.forename: Ilya
authors.initials: I
authors.lastname: Nemenman
authors.forename: Andre
authors.initials: A
authors.lastname: Levchenko
mesh_terms: D016475:3T3 Cells; D051698:Activating Transcription Factor 2 / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D015870:Gene Expression; D017930:Genes, Reporter; D007257:Information Theory; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D059010:Single-Cell Analysis; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D051698:Activating Transcription Factor 2; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse