Modeling formalisms in systems biology

Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future.Research supported by grants SFRH/BD/35215/2007 and SFRH/BD/25506/2005 from the Fundacao para a Ciencia e a Tecnologia (FCT) and the MIT-Portugal Program through the project "Bridging Systems and Synthetic Biology for the development of improved microbial cell factories" (MIT-Pt/BS-BB/0082/2008)

Sample-based Search Methods for Bayes-Adaptive Planning

A fundamental issue for control is acting in the face of uncertainty about the environment. Amongst other things, this induces a trade-off between exploration and exploitation. A model-based Bayesian agent optimizes its return by maintaining a posterior distribution over possible environments, and considering all possible future paths. This optimization is equivalent to solving a Markov Decision Process (MDP) whose hyperstate comprises the agent's beliefs about the environment, as well as its current state in that environment. This corresponding process is called a Bayes-Adaptive MDP (BAMDP). Even for MDPs with only a few states, it is generally intractable to solve the corresponding BAMDP exactly. Various heuristics have been devised, but those that are computationally tractable often perform indifferently, whereas those that perform well are typically so expensive as to be applicable only in small domains with limited structure. Here, we develop new tractable methods for planning in BAMDPs based on recent advances in the solution to large MDPs and general partially observable MDPs. Our algorithms are sample-based, plan online in a way that is focused on the current belief, and, critically, avoid expensive belief updates during simulations. In discrete domains, we use Monte-Carlo tree search to search forward in an aggressive manner. The derived algorithm can scale to large MDPs and provably converges to the Bayes-optimal solution asymptotically. We then consider a more general class of simulation-based methods in which approximation methods can be employed to allow value function estimates to generalize between hyperstates during search. This allows us to tackle continuous domains. We validate our approach empirically in standard domains by comparison with existing approximations. Finally, we explore Bayes-adaptive planning in environments that are modelled by rich, non-parametric probabilistic models. We demonstrate that a fully Bayesian agent can be advantageous in the exploration of complex and even infinite, structured domains

Distributed Particle Filters for Data Assimilation in Simulation of Large Scale Spatial Temporal Systems

Assimilating real time sensor into a running simulation model can improve simulation results for simulating large-scale spatial temporal systems such as wildfire, road traffic and flood. Particle filters are important methods to support data assimilation. While particle filters can work effectively with sophisticated simulation models, they have high computation cost due to the large number of particles needed in order to converge to the true system state. This is especially true for large-scale spatial temporal simulation systems that have high dimensional state space and high computation cost by themselves. To address the performance issue of particle filter-based data assimilation, this dissertation developed distributed particle filters and applied them to large-scale spatial temporal systems. We first implemented a particle filter-based data assimilation framework and carried out data assimilation to estimate system state and model parameters based on an application of wildfire spread simulation. We then developed advanced particle routing methods in distributed particle filters to route particles among the Processing Units (PUs) after resampling in effective and efficient manners. In particular, for distributed particle filters with centralized resampling, we developed two routing policies named minimal transfer particle routing policy and maximal balance particle routing policy. For distributed PF with decentralized resampling, we developed a hybrid particle routing approach that combines the global routing with the local routing to take advantage of both. The developed routing policies are evaluated from the aspects of communication cost and data assimilation accuracy based on the application of data assimilation for large-scale wildfire spread simulations. Moreover, as cloud computing is gaining more and more popularity; we developed a parallel and distributed particle filter based on Hadoop & MapReduce to support large-scale data assimilation