Difference between revisions of "Sarah Carratt 4.12.11"

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==Sources for this Week==
==Sources for this Week==
*[http://www.sciencemag.org/content/298/5594/763.full?sid=b06c10fd-ebcf-4e75-9842-b44d7e650170 Oltvai & Barabasi (2002) ''Science'']
*[http://bioinformatics.oxfordjournals.org/content/early/2004/03/22/bioinformatics.bth173.full.pdf Sontag et al (2004) ''Bioinformatics'']
*[http://www.sciencemag.org/content/298/5594/799.full?ijkey=88vy6NpPKM4iQ Lee ''et al.'' (2002) ''Science'']
*[http://sbie.kaist.ac.kr/ftp/Inferring%20gene%20regulatory%20networks%20from%20temporal%20expression%20profiles%20under%20time-delay%20and%20noise%20%5Bcbac-200708%5D.pdf Kim ''et al.'' (2007) ''Comp Bio Chem'']
*[http://www.nature.com/nature/journal/v431/n7004/full/nature02800.html Harbison ''et al.'' (2004) ''Nature'']
*[http://nar.oxfordjournals.org/content/35/1/279.short Vu and Vohradsky (2007) ''Nucleic Acid Res'']
*[http://www.biomedcentral.com/1471-2105/7/113 MacIsaac ''et al.'' (2006) ''BMC Bioinformatics'']
==Gene Regulation and Modeling==
==Gene Regulation and Modeling==

Latest revision as of 08:32, 14 April 2011

Sources for this Week

Gene Regulation and Modeling

  • Focused on measuring RNA and modeling dynamic behavior of proteins that RNA spins off
  • High activity in RNA should mean high protein behavior
  • Low activity in RNA should mean low protein behavior

Modeling in Network Construction

  • Qualitative, not just quantitative/numbers
  • Active genes working simultaneously → transcription factors
    • Define "simultaneously"
  • Database represents a model built through experiments and literature


  • Define distance metric (this is what it means for two things to be close together)
  • Easily build matrix of closeness once distance is defined
  • Clustering is more subtle
    • time 1 graphed vs time 2...dot plot!
    • two+ clusters that are distinct, separate based on where they fall..."an art"


  • 1's and 0's
  • Changes in G1 produces changes in G3 if that box is 1
  • Arrows in diagram show effector/affectee relationship
  • Called an adjacency matrix → graph theory
  • Graph theory is a way to put structures to pictures?
  • When handed adjacency matrix...which ways do the arrows go?


  • How does quantity of protein present relate to genes?
  • Do we know if relationships are activation or repression?
    • Back to microarrays...up or down?
  • What does activation mean?
    • Positive log fold change
    • Produce more/Do more
    • Increase in rate of change (production = rate↑)
  • What does repression mean?
    • Negative log fold change
    • Slow, stop, reduce synthesis/activity
    • Produce less
    • Decrease in production rate

Network Picture

  • Takes the matrix to cartoon land
  • Provides qualitative information about production
  • All arrows are about production
  • Does the arrow = activation or production?
  • Degradation=decrease contrary to production


  • Production - Degradation
  • Half life is measure of degradation (time of how long it takes half of a sample to degrade)
  • Pure degradation modul
  • x = quantity at time t
  • dx/dt = -λ·x(t)
    • λ=fraction of quantity degraded in unit of time (units = 1/time)
  • Start with fixed amount, X = x(0)
  • x(t) = e-λtX
  • d/dt(e-λt) = -λe-λtX
  • dx/dt(e-λt) = -λe-λtX
  • Half life = tH
    • x(0) = X
    • x(tH)= 1/2X = e-λtHX
    • 1/2= e-λtH
    • 2= eλtH
    • λ=log(2)/tH
      • ln of 2 ≈ 0.69
    • tH = ln(2)/λ


  • Production goes up in presence of x2
  • Move x2 means higher rate
  • What does the graph look like?
    • POSITIVE!!! (duh)
  • Production Functions
    • (A) Linear
      • a +bx
    • (B) Michaelis-Menten
      • Vx/(K+x)
    • (C) Sigmoidal
      • approximates a switch
        • starts near zero, increases slowly, jumps up near saturation value and stays there
      • on-off + transition
        • S(x) = 1/(1+e-x)
        • large numbers are close to 1
        • small numbers close to zero
        • has a symmetry (skew symmetry about a point)


P1/(1+ew2(t2-t2)) - λ1x1(t)