Lecture19_Systemsbio.ppt

Systems Biology Ophelia Venturelli CS374 December 6, 2005 Definition: systems biology Quantitative analysis of components and dynamics of complex biological systems Features of complex systems Nonlinearity Features of complex systems Feedback loops Features of complex systems Open systems (dissipation of energy) Features of complex systems Memory (response history dependent) Features of complex systems Nested (modules have complexity) What is Systems Biology? quantitatively account for these properties different levels of modeling Three tiers Interactomes Deterministic Stochastic Principles which transcend tiers… Principle 1: Modularity Module interacting nodes w/ common function constrained pleiotropy feedback loops, oscillators, amplifiers Principle 2: Recurring circuit elements Network motifs histidine kinase response regulator Principle 3: Robustness Robustness insensitivity to parameter variation Severe constraints on design robustness not present in most designs Aims of systems biology Tier 1: Interactome Which molecules talk to each other in networks? Tier 2: Deterministic What is the average case behavior? Tier 3: Stochastic What is the variance of the system? Aims of systems biology Tier 1 get parts list Tier 2 3 enumerate biochemistry Aims of systems biology Tier 2 3 enumerate biochemistry define network/mathematical relationships compute numerical solutions Aims of systems biology Aims of systems biology Deterministic Ordinary differential equations (ODE’s) Concentration as a function of time only Partial differential equations (PDE’s) Concentration as a function of space and time Stochastic Stochastic update equations Molecule numbers as random variables functions of time Tier 1: Static interactome analysis Tier 1: Static interactome analysis Goals Determine network topology Network statistics Analyze modular structure Tier 1: Static interactome analysis Limitations: Time, space, population average Crude interactions strength type