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Probabilistic Safety and Optimal Control for Survival Analysis of Bacillus Subtilis
Alessandro Abate, Maria Prandini, John Lygeros, Shankar Sastry

Citation
Alessandro Abate, Maria Prandini, John Lygeros, Shankar Sastry. "Probabilistic Safety and Optimal Control for Survival Analysis of Bacillus Subtilis". Proceedings of the 2nd Conference on Foundations of Systems Biology in Engineering, 527-532, September, 2007.

Abstract
The investigation of the stress response network of Bacillus Subtilis ATCC 6633 offers a detailed explanation of how the bacterium reacts to competitive environmental conditions, among the many options, by producing the antibiotic subtilin in order to directly suppress other cells while getting immunized. The mechanisms of this generation are fairly well understood and described by a genetic and protein pathway that involves some non-deterministic interplay between the involved quantities: in particular, the presence of switching modes exhibits the activation/deactivation of certain genes and the production of proteins; these transitions in turn depend non-linearly on the above quantities.

According to the general principles of evolution, we may postulate that the way this pathway functions is according to certain criteria and levels of optimality; in this context optimality is intended as a measure of personal fitness or, in the particular instance, of own survival. In particular, one would expect that the switches in the network happen 'optimally' in the above sense.

In this work, we look at a recently developed dynamical model for the genetic network describing the production of subtilin and propose modifications for the model to bring it in line with other evidence reported in the literature. We obtain a system that presents partially decoupled high-level dynamics (those dealing with the population size and the nutrient level) and low-level ones (those describing the mechanism of generation of subtilin by the single cell). The high-level model is non-linear and deterministic, while the low-level one is piecewise-affine, hybrid and stochastic.

The new model allows one to reinterpret the survival analysis for the single B. subtilis cell and study it as a probabilistic, decentralized safety specification problem over a short time horizon; it is 'probabilistic' because of the certainly stochastic dynamics, as well as according to possible 'trembling' features of the actions; it is 'over a short time horizon' because of the greedy nature of the survival games that are played at this level; it is naturally 'decentralized' because each entity, while optimizing for its own fitness (which depends on global information), does not communicate with the competitors, nor has knowledge of their actions; furthermore, we motivate that the solution of the problem may not be globally optimal.

Using recently developed techniques for probabilistic verification in a stochastic hybrid systems setting, we reinterpret the above probabilistic safety problem as a (stochastic) optimal control one, where the controls are (possibly randomized) functions of the state-space that encode the switches in the network. Finally, the solution of this short-time-horizon, stochastic and decentralized optimal control problem yields the structure of the switching behaviors under study. Matching these outcomes with the data in the literature allows concluding that the corresponding mechanisms in the subtilin production network function with a degree of optimality, according to certain survival criteria.

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Citation formats  
  • HTML
    Alessandro Abate, Maria Prandini, John Lygeros, Shankar
    Sastry. <a
    href="http://chess.eecs.berkeley.edu/pubs/441.html"
    >Probabilistic Safety and Optimal Control for Survival
    Analysis of Bacillus Subtilis</a>, Proceedings of the
    2nd Conference on Foundations of Systems Biology in
    Engineering, 527-532, September, 2007.
  • Plain text
    Alessandro Abate, Maria Prandini, John Lygeros, Shankar
    Sastry. "Probabilistic Safety and Optimal Control for
    Survival Analysis of Bacillus Subtilis". Proceedings of
    the 2nd Conference on Foundations of Systems Biology in
    Engineering, 527-532, September, 2007.
  • BibTeX
    @inproceedings{AbatePrandiniLygerosSastry07_ProbabilisticSafetyOptimalControlForSurvivalAnalysis,
        author = {Alessandro Abate and Maria Prandini and John
                  Lygeros and Shankar Sastry},
        title = {Probabilistic Safety and Optimal Control for
                  Survival Analysis of Bacillus Subtilis},
        booktitle = {Proceedings of the 2nd Conference on Foundations
                  of Systems Biology in Engineering},
        pages = {527-532},
        month = {September},
        year = {2007},
        abstract = {The investigation of the stress response network
                  of Bacillus Subtilis ATCC 6633 offers a detailed
                  explanation of how the bacterium reacts to
                  competitive environmental conditions, among the
                  many options, by producing the antibiotic subtilin
                  in order to directly suppress other cells while
                  getting immunized. The mechanisms of this
                  generation are fairly well understood and
                  described by a genetic and protein pathway that
                  involves some non-deterministic interplay between
                  the involved quantities: in particular, the
                  presence of switching modes exhibits the
                  activation/deactivation of certain genes and the
                  production of proteins; these transitions in turn
                  depend non-linearly on the above quantities.
                  <p>According to the general principles of
                  evolution, we may postulate that the way this
                  pathway functions is according to certain criteria
                  and levels of optimality; in this context
                  optimality is intended as a measure of personal
                  fitness or, in the particular instance, of own
                  survival. In particular, one would expect that the
                  switches in the network happen 'optimally' in the
                  above sense. <p>In this work, we look at a
                  recently developed dynamical model for the genetic
                  network describing the production of subtilin and
                  propose modifications for the model to bring it in
                  line with other evidence reported in the
                  literature. We obtain a system that presents
                  partially decoupled high-level dynamics (those
                  dealing with the population size and the nutrient
                  level) and low-level ones (those describing the
                  mechanism of generation of subtilin by the single
                  cell). The high-level model is non-linear and
                  deterministic, while the low-level one is
                  piecewise-affine, hybrid and stochastic. <p>The
                  new model allows one to reinterpret the survival
                  analysis for the single B. subtilis cell and study
                  it as a probabilistic, decentralized safety
                  specification problem over a short time horizon;
                  it is 'probabilistic' because of the certainly
                  stochastic dynamics, as well as according to
                  possible 'trembling' features of the actions; it
                  is 'over a short time horizon' because of the
                  greedy nature of the survival games that are
                  played at this level; it is naturally
                  'decentralized' because each entity, while
                  optimizing for its own fitness (which depends on
                  global information), does not communicate with the
                  competitors, nor has knowledge of their actions;
                  furthermore, we motivate that the solution of the
                  problem may not be globally optimal. <p>Using
                  recently developed techniques for probabilistic
                  verification in a stochastic hybrid systems
                  setting, we reinterpret the above probabilistic
                  safety problem as a (stochastic) optimal control
                  one, where the controls are (possibly randomized)
                  functions of the state-space that encode the
                  switches in the network. Finally, the solution of
                  this short-time-horizon, stochastic and
                  decentralized optimal control problem yields the
                  structure of the switching behaviors under study.
                  Matching these outcomes with the data in the
                  literature allows concluding that the
                  corresponding mechanisms in the subtilin
                  production network function with a degree of
                  optimality, according to certain survival criteria.},
        URL = {http://chess.eecs.berkeley.edu/pubs/441.html}
    }
    

Posted by Alessandro Abate on 16 Jun 2008.
Groups: chess
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