MOTIVATION: This article presents libRoadRunner 2.0, an extensible, high-performance, cross-platform, open-source software library for the simulation and analysis of models expressed using the systems biology markup language (SBML). RESULTS: libRoadRunner is a self-contained library, able to run either as a component inside other tools via its C++, C and Python APIs, or interactively through its Python or Julia interface. libRoadRunner uses a custom just-in-time (JIT) compiler built on the widely used LLVM JIT compiler framework. It compiles SBML-specified models directly into native machine code for a large variety of processors, making it fast enough to simulate extremely large models or repeated runs in reasonable timeframes. libRoadRunner is flexible, supporting the bulk of the SBML specification (except for delay and non-linear algebraic equations) as well as several SBML extensions such as hierarchical composition and probability distributions. It offers multiple deterministic and stochastic integrators, as well as tools for steady-state, sensitivity, stability and structural analyses. AVAILABILITY AND IMPLEMENTATION: libRoadRunner binary distributions for Windows, Mac OS and Linux, Julia and Python bindings, source code and documentation are all available at https://github.com/sys-bio/roadrunner, and Python bindings are also available via pip. The source code can be compiled for the supported systems as well as in principle any system supported by LLVM-13, such as ARM-based computers like the Raspberry Pi. The library is licensed under the Apache License Version 2.0.

Information processing in artificial neural networks is largely dependent on the nature of neuron models. While commonly used models are designed for linear integration of synaptic inputs, accumulating experimental evidence suggests that biological neurons are capable of nonlinear computations for many converging synaptic inputs via homo- and heterosynaptic mechanisms. This nonlinear neuronal computation may play an important role in complex information processing at the neural circuit level. Here we characterize the dynamics and coding properties of neuron models on synaptic transmissions delivered from two hidden states. The neuronal information processing is influenced by the cooperative and competitive interactions among synapses and the coherence of the hidden states. Furthermore, we demonstrate that neuronal information processing under two-input synaptic transmission can be mapped to linearly nonseparable XOR as well as basic AND/OR operations. In particular, the mixtures of linear and nonlinear neuron models outperform the fashion-MNIST test compared to the neural networks consisting of only one type. This study provides a computational framework for assessing information processing of neuron and synapse models that may be beneficial for the design of brain-inspired artificial intelligence algorithms and neuromorphic systems.

The considerable difficulty encountered in reproducing the results of published dynamical models limits validation, exploration and reuse of this increasingly large biomedical research resource. To address this problem, we have developed Tellurium Notebook, a software system for model authoring, simulation, and teaching that facilitates building reproducible dynamical models and reusing models by 1) providing a notebook environment which allows models, Python code, and narrative to be intermixed, 2) supporting the COMBINE archive format during model development for capturing model information in an exchangeable format and 3) enabling users to easily simulate and edit public COMBINE-compliant models from public repositories to facilitate studying model dynamics, variants and test cases. Tellurium Notebook, a Python-based Jupyter-like environment, is designed to seamlessly inter-operate with these community standards by automating conversion between COMBINE standards formulations and corresponding in-line, human-readable representations. Thus, Tellurium brings to systems biology the strategy used by other literate notebook systems such as Mathematica. These capabilities allow users to edit every aspect of the standards-compliant models and simulations, run the simulations in-line, and re-export to standard formats. We provide several use cases illustrating the advantages of our approach and how it allows development and reuse of models without requiring technical knowledge of standards. Adoption of Tellurium should accelerate model development, reproducibility and reuse.