Probabilistic Boolean Networks英文电子书.pdfVIP

Probabilistic Boolean Networks as Models of Gene Regulatory Networks: Inference, Simulation, Intervention Ilya Shmulevich University of Texas M. D. Anderson Cancer Center Outline of the Presentation Biological motivation Why study genetic networks? Requirements of our models What questions do we want to answer? Boolean Formalism Biological Implications Probabilistic Boolean Networks Dynamics, Uncertainty, Graphical Models, Influence and Sensitivity of Genes, Perturbation, Intervention, Sensitivity Analysis 2 Biological Motivation We’re in the era of holistic biology. Massive amounts of biological data await interpretation: this calls for formal modeling and computational methods; it opens up a window on dynamical and functional characteristics (physiology) of an organism and disease progression. 3 Biological Motivation Genes are not independent. They regulate each other and act collectively. This collective behavior can be observed using microarrays. Interest is shifting to temporal, genome-wide expression profiling. Such studies benefit from microarray technology. e.g. clustering, PCA, multidimensional scaling, network inference. The interrelationships among genes constitute gene regulatory networks. 4 Genetic Network Models: Goals Must incorporate rule-based dependencies between genes Rule-based dependencies may constitute important biological information. Must allow to systematically study global network dynamics In particular, individual gene effects on long-run network behavior. Must be able to cope with uncertainty Small sample size, n