17183751d01 - Bottom-up modeling I: Genetic Network...

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Unformatted text preview: Bottom-up modeling I: Genetic Network Modeling Deciphering the logic of genetic regulation “The next generation of students should learn how to look for ampliFers and logic circuits, as well as to describe and look for molecules and genes.” Hartwell et al. (1999) Nature Roeland Merks Netherlands Institute for Systems Biology Centrum Wiskunde & Informatica Amsterdam http://www.sysbio.nl and http://www.cwi.nl From parts lists and networks to dynamic networks • In the previous lessons you have seen: • How to construct “parts lists” and interaction networks of biological systems • How to analyze these static networks • How can we analyze the dynamics of these networks? Genetic networks Analogy: circuit diagram Genetic networks • Complex regulatory networks between genes and their products control cell behaviors • cell cycle • apoptosis • cell differentiation • cell communication • Detailed model with many parameters • Captures phenomena quantitatively • requires large amounts of data • Might be as difFcult to analyse as real system • “Coarse” model with low complexity • Captures dynamics qualitatively • requires smaller amounts of data • Easier to analyse: new insights Choosing a model: trade-off • “Pluralitas non est ponenda sine necessitate” • Do not assume more than necessary • Model complexity should never be made higher than what is necessary to faithfully “explain the data” • What kind of data do we have and how much? William of Ockham (1280-1349) Ockham’s Razor Reality • Millions possible molecular interactions • Compartments • DNA is transcribed in nucleus, mRNA is translated in cytosol • Protein transport • Molecular crowding: law of mass action does not always work • ... Common simplifcations • Consider only a subset oF genes • Neglect intracellular structure • All molecules in one, mixed compartment • Law oF mass action is valid: no molecular crowding • No stochasticity: large number oF molecules • Retained: concentration oF molecules, reaction rates, e.g. ODE models Boolean networks The logic of networks • Further simpli¡cation • No chemical kinetics • No reaction rates • No concentrations • No translation/transcription • Genes are either ON or OFF • Boolean functions specify genetic interactions “Boolean” gene regulation AND function B A B A Gene transcription if A AND B are present “Boolean” gene regulation OR function A Gene transcription if A OR B are present B A B “Boolean” gene regulation XOR function A Gene transcription if A or B, NOT BOTH are present B A B “Boolean” gene regulation NOT A function Gene transcription if A is NOT present A is repressor B A A B “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A “Boolean” gene regulation Boolean Networks A & !B NOT B AND Inactive Active B A B A B A Oscillator and inhibitor of oscillation! “Generic” Boolean Networks...
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This note was uploaded on 05/30/2010 for the course WE CMBIBI0200 taught by Professor Pierrehilson during the Spring '10 term at Ghent University.

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17183751d01 - Bottom-up modeling I: Genetic Network...

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