Modeling, Analysis, Simulation, and Synthesis of Biomolecular Networks
Abstract
This project under the DARPA BIOCOMP program integrated fundamental scientific investigations in the field of molecular systems biology, algorithm development for biomolecular modeling, and open source, object based software implementation. Major accomplishments were 1) experimental gene knockout strain investigations of the V.fisheri quorum sensing system that yielded a mathematical model of its regulatory proteins, 2) a model of stringent response in E.coli and M.tuberculosis describing the role of enzyme RelMtb, 3) a first example of reachability analysis applied to a biomolecular system (lactose induction), 4) a model of tetracycline resistance that discriminates between two possible mechanisms for tetracycline diffusion through the cell membrane, and 5) a new method for investigating the producibility of a metabolite by a network of chemical reactions from an available set of nutrients using sets of gene knockouts. Accomplishments in algorithm/implementation were 1) reachability and other metabolic analysis tools for non-linear biomolecular networks aiding construction of a hybrid systems-based abstraction, 2) a Systems Biology Markup Language compatible reachability algorithm using a piecewise multi-affine hybrid system method, and 3) a metabolic network producibility analysis algorithm for large scale metabolic networks predicting the possibility of producing a set of metabolites from a set of available nutrients, complementing biomass flux optimization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA459959
Entities
People
- Harvey Ruben
- Oleg Sokolsky
- Vijay Kumar
Organizations
- University of Pennsylvania