arXiv subjects

Herbert M. Sauro

Publications and source records attributed to Herbert M. Sauro.

At least 19 recordsLinked to original sources

arXiv2026

An interactive simulator for integrating biochemical models with experimental data

Biological models based on mathematical simulations (e.g., ordinary differential equations) are hugely beneficial for understanding biological processes and predicting the outcomes of experiments. Such models are built using a variety of sophisticated modeling tools. Unfortunately, the complexity of these tools is often a barrier to use by experimental biologists. To improve the usability and impact of biological models, we have created a desktop platform (DeskIridium) and a web-based simulator (WebIridium, hosted as a GitHub page) that, in combination, provide features that promote ease of use by experimental biologists, including: human-readable editing of models via the Antimony syntax; sliders for adjusting parameter values while simultaneously displaying simulation results in real time; zero-install distribution; AI chat integration; and generation of standalone Python implementations of SBML models to support reproducibility. The desktop version uses the well-established libroadrunner simulation package; the web-based application uses an Emscripten translated version of COPASI. Both simulators are SBML-compatible, allowing users to easily import previously built models or edit existing models using the easy-to-use antimony language. We used modern AI methods for software development and share the lessons we learned. Binaries, source code, and the web interface are available at: https://github.com/sys-bio/IridiumSimulator and https://github.com/sys-bio/WebIridium.

q-bio.MN↗

arXiv2025

EFECT: A Method to Quantify the Reproducibility of Stochastic Simulations

Reproducibility is a fundamental requirement for validating scientific claims in computational research. Stochastic computational models are widely used in fields such as systems biology, financial modeling and environmental sciences. However, achieving reproducibility in stochastic simulations remains challenging, as each run can produce different outcomes. Existing infrastructure and software tools do not address independent reproduction of simulation results. Without independent reproducibility, results and conclusions lack credibility, as it remains unclear whether observed findings reflect model behavior or are artifacts of stochastic variation or an underpowered study. To bridge this gap, we introduce the Empirical Characteristic Function Equality Convergence Test (EFECT), a data-driven method to quantify the reproducibility of stochastic simulation results. EFECT employs empirical characteristic functions to compare reported results with those independently generated by assessing distributional inequality, termed EFECT error. Additionally, we establish the EFECT convergence point, a quantitative metric for determining the required number of simulation runs to achieve an EFECT error value of a priori significance. EFECT is applicable to all bounded, real-valued outputs, regardless of the model type or simulation method that produced them. We tested EFECT with over 40 use cases to demonstrate its broad applicability and effectiveness. EFECT standardizes stochastic simulation reproducibility, establishing a workflow that guarantees reliable results, supporting a wide range of stakeholders, and thereby enhancing validation of stochastic simulation studies, across a model's lifecycle. To promote standardization, we are developing the open-source software library libSSR in multiple programming languages for easy integration of EFECT.

stat.ME↗

arXiv2025

From FAIR to CURE: Guidelines for Computational Models of Biological Systems

Guidelines for managing scientific data have been established under the FAIR principles requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of 'data', we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary set of guidelines. We propose the CURE principles, emphasizing that models should be Credible, Understandable, Reproducible, and Extensible. We delve into each principle, discussing verification, validation, and uncertainty quantification for model credibility; the clarity of model descriptions and annotations for understandability; adherence to standards and open science practices for reproducibility; and the use of open standards and modular code for extensibility and reuse. We outline recommended and baseline requirements for each aspect of CURE, aiming to enhance the impact and trustworthiness of computational models, particularly in biomedical applications where credibility is paramount. Our perspective underscores the need for a more disciplined approach to modeling, aligning with emerging trends such as Digital Twins and emphasizing the importance of data and modeling standards for interoperability and reuse. Finally, we emphasize that given the non-trivial effort required to implement the guidelines, the community moves to automate as many of the guidelines as possible.

q-bio.OT↗

arXiv2023

Design Patterns of Biological Cells

Design patterns are generalized solutions to frequently recurring problems. They were initially developed by architects and computer scientists to create a higher level of abstraction for their designs. Here, we extend these concepts to cell biology in order to lend a new perspective on the evolved designs of cells' underlying reaction networks. We present a catalog of 21 design patterns divided into three categories: creational patterns describe processes that build the cell, structural patterns describe the layouts of reaction networks, and behavioral patterns describe reaction network function. Applying this pattern language to the E. coli central metabolic reaction network, the yeast pheromone response signaling network, and other examples lends new insights into these systems.

q-bio.MN↗

arXiv2023

Use of Interactive Simulations in Fundamentals of Biochemistry, a LibreText Online Educational Resource, to Promote Understanding of Dynamic Reactions

Biology is perhaps the most complex of the sciences, given the incredible variety of chemical species that are interconnected in spatial and temporal pathways that are daunting to understand. Their interconnections lead to emergent properties such as memory, consciousness, and recognition of self and non-self. To understand how these interconnected reactions lead to cellular life characterized by activation, inhibition, regulation, homeostasis, and adaptation, computational analyses and simulations are essential, a fact recognized by the biological communities. At the same time, students struggle to understand and apply binding and kinetic analyses for the simplest reactions such as the irreversible first-order conversion of a single reactant to a product. This likely results from cognitive difficulties in combining structural, chemical, mathematical, and textual descriptions of binding and catalytic reactions. To help students better understand dynamic reactions and their analyses, we have introduced two kinds of interactive graphs and simulations into the online educational resource, Fundamentals of Biochemistry, a multivolume biochemistry textbook that is part of the LibreText collection. One type is available for simple binding and kinetic reactions. The other displays progress curves (concentrations vs time) for both simple reactions and more complex metabolic and signal transduction pathways, including those available through databases using systems biology markup language (SBML) files. Users can move sliders to change dissociation and kinetic constants as well as initial concentrations and see instantaneous changes in the graphs. They can also export data into a spreadsheet for further processing, such as producing derivative Lineweaver-Burk and traditional Michaelis-Menten graphs of initial velocity (v0) vs substrate concentration.

physics.bio-ph↗

arXiv2023

MakeSBML: A tool for converting between Antimony and SBML

We describe a web-based tool, MakeSBML (https://sys-bio.github.io/makesbml/), that provides an installation-free application for creating, editing, and searching the Biomodels repository for SBML-based models. MakeSBML is a client-based web application that translates models expressed in human-readable Antimony to the System Biology Markup Language (SBML) and vice-versa. Since MakeSBML is a web-based application it requires no installation on the user's part. Currently, MakeSBML is hosted on a GitHub page where the client-based design makes it trivial to move to other hosts. This model for software deployment also reduces maintenance costs since an active server is not required. The SBML modeling language is often used in systems biology research to describe complex biochemical networks and makes reproducing models much easier. However, SBML is designed to be computer-readable, not human-readable. We therefore employ the human-readable Antimony language to make it easy to create and edit SBML models.

q-bio.MN↗

arXiv2023

SBcoyote: An Extensible Python-Based Reaction Editor and Viewer

SBcoyote is an open-source cross-platform biochemical reaction viewer and editor released under the liberal MIT license. It is written in Python and uses wxPython to implement the GUI and the drawing canvas. It supports the visualization and editing of compartments, species, and reactions. It includes many options to stylize each of these components. For instance, species can be in different colors and shapes. Other core features include the ability to create alias nodes, alignment of groups of nodes, network zooming, as well as an interactive bird-eye view of the network to allow easy navigation on large networks. A unique feature of the tool is the extensive Python plugin API, where third-party developers can include new functionality. To assist third-party plugin developers, we provide a variety of sample plugins, including, random network generation, a simple auto layout tool, export to Antimony, export SBML, import SBML, etc. Of particular interest are the export and import SBML plugins since these support the SBML level 3 layout and render standard, which is exchangeable with other software packages. Plugins are stored in a GitHub repository, and an included plugin manager can retrieve and install new plugins from the repository on demand. Plugins have version metadata associated with them to make it install plugin updates. Availability: https://github.com/sys-bio/SBcoyote.

q-bio.QM↗

arXiv2023

Adapting Modeling and Simulation Credibility Standards to Computational Systems Biology

Computational models are increasingly used in high-impact decision making in science, engineering, and medicine. The National Aeronautics and Space Administration (NASA) uses computational models to perform complex experiments that are otherwise prohibitively expensive or require a microgravity environment. Similarly, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have began accepting models and simulations as form of evidence for pharmaceutical and medical device approval. It is crucial that computational models meet a standard of credibility when using them in high-stakes decision making. For this reason, institutes including NASA, the FDA, and the EMA have developed standards to promote and assess the credibility of computational models and simulations. However, due to the breadth of models these institutes assess, these credibility standards are mostly qualitative and avoid making specific recommendations. On the other hand, modeling and simulation in systems biology is a narrow domain and several standards are already in place. As systems biology models increase in complexity and influence, the development of a credibility assessment system is crucial. Here we review existing standards in systems biology, credibility standards in other science, engineering, and medical fields, and propose the development of a credibility standard for systems biology models.

q-bio.MN↗

arXiv2022

SBMLDiagrams: A python package to process and visualize SBML layout and render

Summary: The Systems Biology Markup Language (SBML) is an extensible standard format for exchanging biochemical models. One of the extensions for SBML is the SBML Layout and Render package. This allows modelers to describe a biochemical model as a pathway diagram. However, up to now there has been little support to help users easily add and retrieve such information from SBML. In this application note, we describe a new Python package called SBMLDiagrams. This package allows a user to add layout and render information or retrieve it using a straightforward Python API. The package uses skia-python to support the rendering of the diagrams, allowing export to commons formats such as PNG or PDF. Availability: SBMLDiagrams is publicly available and licensed under the liberal MIT open-source license. The package is available for all major platforms. The source code has been deposited at GitHub (github.com/sys-bio/SBMLDiagrams). Users can install the package using the standard pip installation mechanism: pip install SBMLDiagrams. Contact: hsauro@uw.edu.

q-bio.QM↗

arXiv2022

SBbadger: Biochemical Reaction Networks with Definable Degree Distributions

Motivation: An essential step in developing computational tools for the inference, optimization, and simulation of biochemical reaction networks is gauging tool performance against earlier efforts using an appropriate set of benchmarks. General strategies for the assembly of benchmark models include collection from the literature, creation via subnetwork extraction and de novo generation. However, with respect to biochemical reaction networks, these approaches and their associated tools are either poorly suited to generate models that reflect the wide range of properties found in natural biochemical networks or to do so in numbers that enable rigorous statistical analysis. Results: In this work we present SBbadger, a python-based software tool for the generation of synthetic biochemical reaction or metabolic networks with user-defined degree distributions, multiple available kinetic formalisms, and a host of other definable properties. SBbadger thus enables the creation of benchmark model sets that reflect properties of biological systems and generate the kinetics and model structures typically targeted by computational analysis and inference software. Here we detail the computational and algorithmic workflow of SBbadger, demonstrate its performance under various settings, provide samples outputs, and compare it to currently available biochemical reaction network generation software.

q-bio.MN↗

arXiv2022

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line, and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML, and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations.

q-bio.QM↗

arXiv2022

libRoadRunner 2.0: A High-Performance SBML Simulation and Analysis Library

Motivation: This paper presents libRoadRunner 2.0, an extensible, high-performance, cross-platform, open-source software library for the simulation and analysis of models expressed using Systems Biology Markup Language SBML). Results: libRoadRunner is a self-contained library, able to run both as a component inside other tools via its C++ and C bindings, and 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 appropriate for solving extremely large models or repeated runs. libRoadRunner is flexible, supporting the bulk of the SBML specification (except for delay and nonlinear algebraic equations) and including several SBML extensions such as composition and distributions. It offers multiple deterministic and stochastic integrators, as well as tools for steady-state, sensitivity, stability analysis, and structural analysis of the stoichiometric matrix. Availability: libRoadRunner binary distributions are available for Mac OS X, Linux, and Windows. The library is licensed under the Apache License Version 2.0. libRoadRunner is also available for ARM-based computers such as the Raspberry Pi and can in principle be compiled on any system supported by LLVM-13. http://sys-bio.github.io/roadrunner/index.html provides online documentation, full build instructions, binaries, and a git source repository.

q-bio.QM↗

arXiv2021

The Practice of Ensuring Repeatable and Reproducible Computational Models

Recent studies have shown that the majority of published computational models in systems biology and physiology are not repeatable or reproducible. There are a variety of reasons for this. One of the most likely reasons is that given how busy modern researchers are and the fact that no credit is given to authors for publishing repeatable work, it is inevitable that this will be the case. The situation can only be rectified when government agencies, universities and other research institutions change policies and that journals begin to insist that published work is in fact at least repeatable if not reproducible. In this chapter guidelines are described that can be used by researchers to help make sure their work is repeatable. A scoring system is suggested that authors can use to determine how well they are doing.

q-bio.OT↗

arXiv2021

Dynamics and Sensitivity of Signaling Pathways

Signaling pathways serve to communicate information about extracellular conditions into the cell, to both the nucleus and cytoplasmic processes to control cell responses. Genetic mutations in signaling network components are frequently associated with cancer and can result in cells acquiring an ability to divide and grow uncontrollably. Because signaling pathways play such a significant role in cancer initiation and advancement, their constituent proteins are attractive therapeutic targets. In this review, we discuss how signaling pathway modeling can assist with identifying effective drugs for treating diseases, such as cancer. An achievement that would facilitate the use of such models is their ability to identify controlling biochemical parameters in signaling pathways, such as molecular abundances and chemical reaction rates, because this would help determine effective points of attack by therapeutics.

q-bio.MN↗

arXiv2021

SED-ML Validator: tool for debugging simulation experiments

Summary: More sophisticated models are needed to address problems in bioscience, synthetic biology, and precision medicine. To help facilitate the collaboration needed for such models, the community developed the Simulation Experiment Description Markup Language (SED-ML), a common format for describing simulations. However, the utility of SED-ML has been hampered by limited support for SED-ML among modeling software tools and by different interpretations of SED-ML among the tools that support the format. To help modelers debug their simulations and to push the community to use SED-ML consistently, we developed a tool for validating SED-ML files. We have used the validator to correct the official SED-ML example files. We plan to use the validator to correct the files in the BioModels database so that they can be simulated. We anticipate that the validator will be a valuable tool for developing more predictive simulations and that the validator will help increase the adoption and interoperability of SED-ML. Availability: The validator is freely available as a webform, HTTP API, command-line program, and Python package at https://run.biosimulations.org/utils/validate and https://pypi.org/project/biosimulators-utils. The validator is also embedded into interfaces to 11 simulation tools. The source code is openly available as described in the Supplementary data. Contact: karr@mssm.edu

q-bio.QM↗

arXiv2021

Real-Time Interactive Modeling and Simulation in Biological Physics and Active Matter with Mechanica

Modeling and simulation (M&S) has revolutionized the way modern engineered products are designed, tested and evaluated. Yet modeling and simulation is much less frequently applied in the study of natural biological and active matter systems. Two of the greatest challenges in applying M\&S approaches to natural biological systems are (1) difficulty in specifying a model, and developing a simulation from it, and (2) tuning and optimizing parameters. Here we address the first challenge directly, and develop a software library that can lead to progress in the second.

q-bio.SC↗

arXiv2021

Practical Resources for Enhancing the Reproducibility of Mechanistic Modeling in Systems Biology

Although reproducibility is a core tenet of the scientific method, it remains challenging to reproduce many results. Surprisingly, this also holds true for computational results in domains such as systems biology where there have been extensive standardization efforts. For example, Tiwari et al. recently found that they could only repeat 50% of published simulation results in systems biology. Toward improving the reproducibility of computational systems research, we identified several resources that investigators can leverage to make their research more accessible, executable, and comprehensible by others. In particular, we identified several domain standards and curation services, as well as powerful approaches pioneered by the software engineering industry that we believe many investigators could adopt. Together, we believe these approaches could substantially enhance the reproducibility of systems biology research. In turn, we believe enhanced reproducibility would accelerate the development of more sophisticated models that could inform precision medicine and synthetic biology.

q-bio.QM↗

arXiv2019

A Commentary on the Linearity and Time-Invariance of ODE-Based Systems

Linear time-invariant (LTI) systems appear frequently in natural sciences and engineering contexts. Many LTI systems are described by ordinary differential equations (ODEs). For example, biological gene regulation, analog filter circuits, and simple mechanical, electrical, and hydraulic systems can all be described with varying approximations as LTI systems using ODEs. While linearity and time-invariance are straightforward to demonstrate for closed-form system definitions, determining whether an ODE describes a system with LTI properties is less obvious and rarely discussed in depth in the literature. Complications arise due to slightly different definitions of linearity in different contexts. This commentary is intended to provide clarity on this subtle point, and act as an instructional aid or educational supplement.

eess.SY↗