BiPSim: a flexible and generic stochastic simulator for polymerization processes

Detailed whole-cell modeling requires an integration of heterogeneous cell processes having different modeling formalisms, for which whole-cell simulation could remain tractable. Here, we introduce BiPSim, an open-source stochastic simulator of template-based polymerization processes, such as replication, transcription and translation. BiPSim combines an efficient abstract representation of reactions and a constant-time implementation of the Gillespie’s Stochastic Simulation Algorithm (SSA) with respect to reactions, which makes it highly efficient to simulate large-scale polymerization processes stochastically. Moreover, multi-level descriptions of polymerization processes can be handled simultaneously, allowing the user to tune a trade-off between simulation speed and model granularity. We evaluated the performance of BiPSim by simulating genome-wide gene expression in bacteria for multiple levels of granularity. Finally, since no cell-type specific information is hard-coded in the simulator, models can easily be adapted to other organismal species. We expect that BiPSim should open new perspectives for the genome-wide simulation of stochastic phenomena in biology.

An automated system repair framework with signal temporal logic

We present an automated system repair framework for cyber-physical systems. The proposed framework consists of three main steps: (1) system simulation and fault detection to generate a labeled dataset, (2) identification of the repairable temporal properties leading to the faulty behavior and (3) repairing the system to avoid the occurrence of the cause identified in the second step. We express the cause as a past time signal temporal logic (ptSTL) formula and present an efficient monotonicity-based method to synthesize a ptSTL formula from a labeled dataset. Then, in the third step, we modify the faulty system by removing all behaviors that satisfy the ptSTL formula representing the cause of the fault. We apply the framework to two rich modeling formalisms: discrete-time dynamical systems and timed automata. For both of them, we define repairable formulae, the corresponding repair procedures, and illustrate them over case studies.

An Efficient Library for Reliability Block Diagram Evaluation

Reliability Block Diagrams (RBDs) are widely used in reliability engineering to model how the system reliability depends on the reliability of components or subsystems. In this paper, we present librbd, a C library providing a generic, efficient and open-source solution for time-dependent reliability evaluation of RBDs. The library has been developed as a part of a project for reliability evaluation of complex systems through a layered approach, combining different modeling formalisms and solution techniques at different system levels. The library achieves accuracy and efficiency comparable to, and mostly better than, those of other well-established tools, and it is well designed so that it can be easily used by other libraries and tools.

Survey of Engineering Models for Systems Biology

In recent years, the field of systems biology has emerged from a confluence of an increase both in molecular biotechnology and in computing storage and power. As a discipline, systems biology shares many characteristics with engineering. However, before the benefits of engineering-based modeling formalisms and analysis tools can be applied to systems biology, the engineering discipline(s) most related to systems biology must be identified. In this paper, we identify the cell as an embedded computing system and, as such, demonstrate that systems biology shares many aspects in common with computer systems engineering, electrical engineering, and chemical engineering. This realization solidifies the grounds for using modeling formalisms from these engineering subdisciplines to be applied to biological systems. While we document several examples where this is already happening, our goal is that identifying the cell as an embedded computing system would motivate and facilitate further discovery through more widespread use of the modeling formalisms described here.