System Biology
whole > sum of its part
What system biology not... NOT a black office, NOT a Spherical Cow',
A matter of sacle- physics, chemistry , biology
A Fundamental Difference-- physics, chemistry= predictive, but, biology= observational
Making biology a predictive science
why do we need computational modelling?
A new way of drug design- system focus<- target focus<- legend focus Reconstruction of Metabolic Networks Practice of systems biology Stoichiometric Analysis- capture the structure of metabolic network, does not require quntitative kinetic parameters, FBA (Flux balance analysis) Work Flow of FBA -- Development of pathway model-> computation of stoichiometric matrix-> FBA-->in silico gene deletions-> drug perturbations-> identification of protein essential to pathway-> Drug target
Mycolic Acid Biosynthesis Pathway
Reactome Modelling -- Pathway Modelling (FBA), Network Modelling
Reaction Networks: Comparative Analysis
targetTB: Target Identification Pipeline
Network Analysis- Node deletions: change in netwok parameters; Lethal Deletions
Interactome Construction
Structure Analysis
PocketDepth: Binding pocket detection
PocketMatch- A new algorithm for Binding site comparison
Protein-Protein Influence Matrix: identify maximally connected code; Preliminary analysis shows hub involvement.
High Order Interactions: Pathway-Pathway; Process-Process
Pathways to Drug Resistant
Model Summary: model construction from litreature, Boolean construction, 75 nodes are present.
State MAP for simulations
MAP of single & double knock-outs
work flow- host pathogen modelling: advantage of modelling- bird's eye view for host-pathogen interplay
Genomics-> Proteomics-> System Biology
Friday, April 9, 2010
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