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We introduce Catalyst.jl, a flexible and feature-filled Julia library for modeling and high performance simulation of chemical reaction networks (CRNs). Catalyst acts as both a domain-specific language and an intermediate representation for symbolically encoding CRN models as Julia-native objects. This enables a pipeline of symbolically specifying, analyzing, and modifying reaction networks; converting Catalyst models to symbolic representations of concrete mathematical models; and generating compiled code for use in numerical solvers. Currently Catalyst supports conversion to symbolic discrete stochastic chemical kinetics (jump process), chemical Langevin (stochastic differential equation), and mass-action reaction rate equation (ordinary differential equation) models. Leveraging ModelingToolkit.jl and Symbolics.jl, Catalyst models can be analyzed, simplified, and compiled into optimized representations for use in a broad variety of numerical solvers. The performance of the numerical solvers Catalyst targets is illustrated across a variety of reaction networks by benchmarking stochastic simulation algorithm and ODE solver performance. We demonstrate the extendability and composability of Catalyst by highlighting both how it can compose with a variety of Julia libraries, and how existing open source projects have extended the intermediate representation. These benchmarks demonstrate significant performance improvements compared to several popular reaction network simulators.

AO_SCPLOWBSTRACTC_SCPLOWPharmacometric modeling establishes causal quantitative relationship between administered dose, tissue exposures, desired and undesired effects and patients risk factors. These models are employed to de-risk drug development and guide precision medicine decisions. Recent technological advances rendered collecting real-time and detailed data easy. However, the pharmacometric tools have not been designed to handle heterogeneous, big data and complex models. The estimation methods are outdated to solve modern healthcare challenges. We set out to design a platform that facilitates domain specific modeling and its integration with modern analytics to foster innovation and readiness to data deluge in healthcare. New specialized estimation methodologies have been developed that allow dramatic performance advances in areas that have not seen major improvements in decades. New ODE solver algorithms, such as coefficient-optimized higher order integrators and new automatic stiffness detecting algorithms which are robust to frequent discontinuities, give rise to up to 4x performance improvements across a wide range of stiff and non-stiff systems seen in pharmacometric applications. These methods combine with JIT compiler techniques and further specialize the solution process on the individual systems, allowing statically-sized optimizations and discrete sensitivity analysis via forward-mode automatic differentiation, to further enhance the accuracy and performance of the solving and parameter estimation process. We demonstrate that when all of these techniques are combined with a validated clinical trial dosing mechanism and non-compartmental analysis (NCA) suite, real applications like NLME parameter estimation see run times halved while retaining the same accuracy. Meanwhile in areas with less prior optimization of software, like optimal experimental design, we see orders of magnitude performance enhancements. Together we show a fast and modern domain specific modeling framework which lays a platform for innovation via upcoming integrations with modern analytics.