Abstract. Biomedical research results are being published at a high rate, and with existing search engines, the vast amount of published work is usually easily accessible. However, reproducing published results, either experimental data or observations is often not viable. In this work, we propose a framework to overcome some of the issues of reproducing previous research, and to ensure re-usability of published information. We present here a framework that utilizes the results from state-of-theart biomedical literature mining, biological system modeling and analysis techniques, and provides means to scientists to assemble and reason about information from voluminous, fragmented and sometimes inconsistent literature. The overall process of automated reading, assembly and reasoning can speed up discoveries from the order of decades to the order of hours or days. Our framework described here allows for rapidly conducting thousands of in silico experiments that are designed as part of this process.

The focus of pancreatic cancer research has been shifted from pancreatic cancer cells towards their microenvironment, involving pancreatic stellate cells that interact with cancer cells and influence tumor progression. To quantitatively understand the pancreatic cancer microenvironment, we construct a computational model for intracellular signaling networks of cancer cells and stellate cells as well as their intercellular communication. We extend the rule-based BioNetGen language to depict intra-and inter-cellular dynamics using discrete and continuous variables respectively. Our framework also enables a statistical model checking procedure for analyzing the system behavior in response to various perturbations. The results demonstrate the predictive power of our model by identifying important system properties that are consistent with existing experimental observations. We also obtain interesting insights into the development of novel therapeutic strategies for pancreatic cancer.

In this paper we describe a new tool, SReach, which solves probabilistic bounded reachability problems for two classes of stochastic hybrid systems. The first one is (nonlinear) hybrid automata with parametric uncertainty. The second one is probabilistic hybrid automata with additional randomness for both transition probabilities and variable resets. Standard approaches to reachability problems for linear hybrid systems require numerical solutions for large optimization problems, and become infeasible for systems involving both nonlinear dynamics over the reals and stochasticity. Our approach encodes stochastic information by using random variables, and combines the randomized sampling, a δ-complete decision procedure, and statistical tests. SReach utilizes the δ-complete decision procedure to solve reachability problems in a sound manner, i.e., it always decides correctly if, for a given assignment to all random variables, the system actually reaches the unsafe region. The statistical tests adapted guarantee arbitrary small error bounds between probabilities estimated by SReach and real ones. Compared to standard simulation-based methods, our approach supports non-deterministic branching, increases the coverage of simulation, and avoids the zero-crossing problem. We demonstrate our method's feasibility by applying SReach to three representative biological models and to additional benchmarks for nonlinear hybrid systems with multiple probabilistic system parameters.

We consider model checking of Qualitative Networks, a popular formalism for modeling signal transduction networks in biology. One of the unique features of qualitative networks, due to them lacking initial states, is that of "reducing reachability sets". Simply put, a state that is not visited after i steps will not be visited after i ′ steps for every i ′ > i. We use this feature to create a compact representation of all the paths of a qualitative network of a certain structure. Combining this compact path representation with LTL model checking leads to significant acceleration in performance. In particular, for a recent model of Leukemia, our approach works at least 5 times faster than the standard approach and up to 100 times faster in some cases. Our approach enhances the iterative hypothesis-driven experimentation process used by biologists, enabling fast turnaround of executable biological models.

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