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Different types of Biological Networks. Network. Metabolic. Protein Interaction. Transcriptional. Nodes Links. Transcription factor Target genes. Metabolites. Proteins. Enzymatic conversion. Transcriptional Interaction. Physical Interaction. Interaction. Protein-Protein. - PowerPoint PPT Presentation

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  • Different types of Biological Networks

  • Finding Local properties of Biological Networks: MotifsNetwork motifs are recurrent circuit elements.We can study a network by looking at its parts (or motifs)How many motifs are in the network?

  • Finding Local properties of Biological Networks: Motifs

  • Finding Local properties of Biological Networks: Motifs

  • Finding Local properties of Biological Networks: Motifs

  • Finding Local properties of Biological Networks: Motifs

  • What are these motifs?What biological relevance they have?Finding Local properties of Biological Networks: Motifs

  • Autoregulatory loop The probability of having autoregulatory loops in a random network is ~ 0 !!!!.Transcription networks: The regulation of a gene by its own product.Protein-Protein interaction network: dimerization

  • Autoregulatory loop Positive autoregulationFast time-rise of protein levelNegative autoregulationStable steady stateWhat is the effect of Autoregulatory loops on gene expression levels?

  • Three-node loops There are 13 possible structures with 3 nodesFeed forward loopFeedback loopBut in biological networks you can find only 2!

  • Feed Forward loops

  • Coherent Feed Forward Loop in flagella biosynthesisA transcription coherent FFL motif ensuresThat flagella is synthesized only under appropriate conditions

  • Incoherent Feed Forward Loop in sporulationA transcription incoherent FFL motif produces transient gene expression

  • Feed Back Loops in circadian expression Feed back loops can produce oscillation in gene expressionThe Drosophila CWO geneKadener 2007, Genes and Dev.

  • Single Input Module (SIMs)The SIMs are common in sensory transcription networks:

    Genes from a same Pathway (Arginine synthesis).Genes responding to stress (DNA repair).Genes that assemble a same biological machine (ribosomal genes).

  • Single Input Module (SIM)

    The SIMs can generate temporal programs of expression:Last-In First-Out (LIFO) Program

  • LIFO Program in ArginineBiosynthesis

  • First-In First-Out (FIFO) ProgramKxz1>Kxz2>Kxz3Kxz1
  • Where SIMs meet FFLsTwo interconnected SIMs can be viewed as a multi output FFL

  • Multi-input FFL in Neuronal Networks FLPASHAVDAVANose TouchNoxious ChemicalsNose TouchBackward movement

  • Dense Overlapping Regulon (DOR)X1X2Y1Y2The DORs are more dense than randomly expected

  • How do Network Motifs Integrate?The E.coli Transcription Network (partial)A single DOR LayerA Master Regulators Layer (lots of Auto-Reg.)

  • SummaryNetwork motifs can function inseveral biological processes (sensory systems, development).different time scales (milliseconds, cell generations).

    Network motifs can produce temporal programs (LIFO, FIFO, oscillation).

    Different kinds of network may interact to generate regulation

    *Biological networks show patterns, order.Part of the patterns are better for attending different biological functionsGreen: transcriptional regulationRed: transcriptional regulation and protein-protein interactionDashed line: pure protein-protein interaction*In the early 1970s, intercity coaxial transmission systems, including L-carrier, used feed-forward amplifiers to diminish linear distortion. This more complex method allowed wider bandwidth than earlier feedback systems. Optical fiber, however, made such systems obsolete before many were bui *A SIM is composed of one master regulator and n number of targetsFor example a TF:controlling enzymes from a same pathwaygenes that respond to a same stress (DNA damage repair for ex)Reibosomal genesComon Sensory Transcription Networks *Figure3.Promoter activity profiles of the nine arginine biosynthesis operons. Lux reporter strains were grown in defined medium containing all amino acids and diluted into the same medium lacking arginine. Shown is the ratio of Lux activity to absorbance at each time point divided by the highest ratio for each strain. Blue and red indicate low and high expression, respectively. The pathway diagram illustrates the metabolic steps of the arginine biosynthesis pathway and the dashed arrows indicate the stages at which each gene product participates. Similar results were obtained using GFP reporter strains. *The OR gate allows expression even if X is briefly lost*In c elegans the synaptic conections between 300 neurons were mapedThe motifs (FFL) are as known fronm transcription networks but tile scales a re miliseconds, in comparison from minutes or hoursFFL perfomr information processes on noisy signalsBoth need to cenvey information on sensory componentsThe most comon generalizatin in transcription networks is the multy output ffl, in neuronal netwros it is the multi inputThis is the reflex loop from c elegans*DOR is a row of input TFs that regulate a set of output genes in a densely overlapping way.Not every input regulates every outputHowever the wiring is denser than randomly expected

    *A single DOR Layer: DORS are never inputs or outputs of other DORS

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