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Systems Biology

Systems Biology

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Published by sap7
While in the past it was more common to make preprints, algorithms and
software freely available, authors have become more protective of their
work. I do not know whether this is a re
ection of the increased competition
for recognition or the pressure to commercialise research results.
By making these notes available I hope to receive information about errors,
misconceptions, missing references or acknowledgment, and suggestions to
improve the text. In the modern world of publishing one also feels a need
to clarify that the author makes no warranty of any kind, expressed or
implied, with regard to programs, algorithms, theoretical concepts, or the
documentation contained in this manuscript. The author shall not be liable
in any event for incidental or consequential damages in connection with, or
arising out of, the use of the material provided here.
While in the past it was more common to make preprints, algorithms and
software freely available, authors have become more protective of their
work. I do not know whether this is a re
ection of the increased competition
for recognition or the pressure to commercialise research results.
By making these notes available I hope to receive information about errors,
misconceptions, missing references or acknowledgment, and suggestions to
improve the text. In the modern world of publishing one also feels a need
to clarify that the author makes no warranty of any kind, expressed or
implied, with regard to programs, algorithms, theoretical concepts, or the
documentation contained in this manuscript. The author shall not be liable
in any event for incidental or consequential damages in connection with, or
arising out of, the use of the material provided here.

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Published by: sap7 on Feb 28, 2010
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08/05/2013

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Olaf Wolkenhauer
28th January 2010
c
Copyright O.Wolkenhauer. All rights reserved. This work may not be translated or copied in whole orin part without permission of the author. Distribution or use in connection with any form of electronicstorage, computer software or internet technology is only allowed with permission of the author.
 
This is a draft manuscript
While in the past it was more common to make preprints, algorithms andsoftware freely available, authors have become more protective of theirwork. I do not know whether this is a reflection of the increased com-petition for recognition or the pressure to commercialise research results.By making these notes available I hope to receive information about errors,misconceptions, missing references or acknowledgment, and suggestions toimprove the text. In the modern world of publishing one also feels a needto clarify that the author makes no warranty of any kind, expressed orimplied, with regard to programs, algorithms, theoretical concepts, or thedocumentation contained in this manuscript. The author shall not be liablein any event for incidental or consequential damages in connection with, orarising out of, the use of the material provided here.
 
Contents
1.1 The Systems Biology Approach. . . . . . . . . . . . . . . . . . . . . . . . 31.1.1 Kinds of models. . . . . . . . . . . . . . . . . . . . . . . . . . . . 51.1.1.1 Statistical modelling: Testing for differences. . . . . . . 61.1.1.2 Associations and regression. . . . . . . . . . . . . . . . . 121.1.1.3 Time series analysis. . . . . . . . . . . . . . . . . . . . . 141.1.1.4 Kinetic modelling. . . . . . . . . . . . . . . . . . . . . . 171.1.2 Systems Theory. . . . . . . . . . . . . . . . . . . . . . . . . . . . 211.1.3 Differential equations. . . . . . . . . . . . . . . . . . . . . . . . . 311.1.4 Dynamic Systems Theory. . . . . . . . . . . . . . . . . . . . . . . 351.1.5 Dealing with uncertainty. . . . . . . . . . . . . . . . . . . . . . . 401.2 Dynamical Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461.2.1 Overview - Dynamical Analysis. . . . . . . . . . . . . . . . . . . . 461.2.2 Stability Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . 461.2.3 Network-Topological Analysis. . . . . . . . . . . . . . . . . . . . 491.2.4 Bifurcation Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . 501.2.5 Reachability (of states) and Controllability (of systems). . . . . . 511.2.6 Distinguishability (of states) and Observability (of systems). . . 511.2.7 Robustness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521.2.8 Sensitivity analysis. . . . . . . . . . . . . . . . . . . . . . . . . . 531.2.9 Model Reduction. . . . . . . . . . . . . . . . . . . . . . . . . . . 541.2.10 Sloppiness/ Sloppy Parameter Sensitivity. . . . . . . . . . . . . . 561.2.11 Identifiability of Parameters. . . . . . . . . . . . . . . . . . . . . 571.2.12 Distinguishability of Model Structures. . . . . . . . . . . . . . . . 581.2.13 Generalized Modelling. . . . . . . . . . . . . . . . . . . . . . . . 581.3 The Organisation of Living Cells. . . . . . . . . . . . . . . . . . . . . . . 591.3.1 Structural Organisation. . . . . . . . . . . . . . . . . . . . . . . . 631.3.2 Functional Organisation. . . . . . . . . . . . . . . . . . . . . . . . 651.3.2.1 Signalling by G-protein-linked receptors. . . . . . . . . . 711.3.2.2 Signalling by tyrosine kinase receptors. . . . . . . . . . . 711.3.2.3 Interaction- and pathway maps. . . . . . . . . . . . . . . 731.3.2.4 Temporal aspects. . . . . . . . . . . . . . . . . . . . . . 741.4 Cell Chemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 751.5 Cell Signalling. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79iii

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