Professional Documents
Culture Documents
Pathway Logic
Azmat Ali Khan1, Jamil Ahmad2
1,2
INTRODUCTION
Cell signal transduction occurs when cell responds to some
external stimulus. This process involves number of chemical
modifications that form a cascade of information[9]. This
information propagates downstream through stimulation and
inhibition. This cascade has evolved over the time to show
divergence and the crosstalk between signaling pathways.
These signaling pathways control plethora of processes like
protein synthesis, lipid synthesis, cell growth and proliferation
etc.
Signaling pathways have been modeled using diverse
formalism. Ordinary Differential Equation (ODE) modeling is
widely used to capture the dynamic behavior of the process. A
set of ODEs are solved simultaneously to predict the behavior
in time space. This modeling approach provides very useful
insight in terms of concentrations of chemical species involved
in signaling. On the basis of concentrations, the relative role of
each chemical compound can be ascertained. ODE modeling
involves number of reaction rates and constants. These reaction
rates and constants are usually difficult to find and act as bottle
neck in this type of modeling.
Stochastic modeling involves relative probabilities of
reactions or population of chemical compounds. Main
drawback of this technique is that results vary somewhat with
the change in size of population of chemical compounds. Large
population of chemicals produce better results but at the same
time combinatorial explosion restricts a fairly good population
size.
Hybrid systems techniques are important for modeling
signaling pathways where one wants to capture both
]
[
[
|
|
[
]
]
D. RAC1
RAC1 regulate a diverse range of cellular processes,
including the control of cytoskeletal reorganization and protein
activation. It also plays a critical role in control of cell
morphology and apoptosis signaling.
E. Forkhead box (FOXO)
FOXO proteins are a family of transcription factors that
play important roles in regulating cell growth, proliferation,
differentiation, and longevity. Many FOXO proteins are
important to embryonic development.
Subnets are obtained for said goals and a careful
comparison is made. After examination of these comparisons
following crosstalk are identified.
A. Phosphatidylinositide 3-kinases(PI3K)
PI3K act as a crosstalk between mTOR and RAC1
pathways. Pi3K directly activates RAC1 whereas the activation
of mTOR takes place through two paths. Pi3K activates AKT1
that in turn activates mTOR. In second pathPi3K activates
AKT1 which triggers the activation of TSC and RhEB that
activates mTOR. This shows that AKT1 is involved in both
paths.
REFERENCES
[1] Manuel Clavel, Francisco Duran, Steven Eker, Patrick Lincoln,
Narciso Marti-oliet, Jose Meseguer, and Carolyn Talcott. Maude
manual (version 2.4), 2008.
[2] Joshua Colvin, Michael I. Monine, James R. Faeder, William
S.Hlavacek, Daniel D. Von Ho_, and Richard G. Posner.
Simulation of large-scale rule-based models. Bioinformatics,
25(7):910-917, 2009.
[3] Araki E, Lipes MA, Patti ME, Bruning JC, Haag B 3rd, Johnson
RS, and Kahn CR. Alternate Pathway of insulin signaling in
targeted disruption of the IRS-1 gene. Nature, 372:186{190,
1994.
[4] Steven Eker, Merrill Knapp, Keith Laderoute, Patrick Lincoln,
Jose Meseguer, and Kemal Sonmez. Pathway logic: Symbolic
analysis of biological signaling. In In Proceedings of the Pacific
Symposium on Biocomputing, pages 400-412, 2002.
[5] Steven Eker, Merrill Knapp, Keith Laderoute, Patrick Lincoln,
and Carolyn Talcott. Pathway logic: Executable models of
biological networks. In In Fourth International Workshop on
Rewriting Logic and Its Applications, year = 2002, pages = 71,
publisher = Elsevier.
[6] Mason and C. L. Talcott. The InterOperability Platform and
IMaude:An interactive extension of Maude. Electronic Notes in
Theoretical Computer Science. Elsevier, 7:-, 2004.
[7] Georgios Pavlopoulos, Anna-Lynn Wegener, and Reinhard
Schneider. A survey of visualization tools for biological network
analysis. BioData Mining, 1(1):12, 2008.
[8] Carolyn Talcott, Steven Eker, Patrick Lincoln, and Keith Laderoute. Pathway logic modeling of protein functional domains in
signal transduction. In In Proceedings of the Pacific Symposium
on Biocomputing, pages 568-580, 2004.
[9] Cullen M. Taniguchi, Brice Emanuelli, and C. Ronald Kahn.
Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol, 7:85-96, 2006.
[10] T.A. Yap, M.D. Garrett, M.I. Walton, F. Raynaud, J.S.
de Bono, and P. Workman. Targeting the pi3k-akt-mtor pathway: progress, pitfalls, and promises. Curr Opin Pharmacol,
8(4):393-412, 2008.
[11] Tseng YH, Butte AJ, Kokkotou E, Yechoor VK, Taniguchi CM,
Kriauciunas KM, Cypess AM, Niinobe M, Yoshikawa K, Patti
ME, and Kahn CR. Prediction of preadopicyte di_erentiation
by gene expression reveals role of insuline receptor substrate
and necdin. Nature Cell Biol., 7:601-611, 2005