{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:27:53Z","timestamp":1772159273969,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["GM123032-04"],"award-info":[{"award-number":["GM123032-04"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1933453"],"award-info":[{"award-number":["1933453"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac770","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T17:15:56Z","timestamp":1670433356000},"source":"Crossref","is-referenced-by-count":36,"title":["libRoadRunner 2.0: a high performance SBML simulation and analysis library"],"prefix":"10.1093","volume":"39","author":[{"given":"Ciaran","family":"Welsh","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Washington , Seattle, WA 98195, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6738-9979","authenticated-orcid":false,"given":"Jin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington , Seattle, WA 98195, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7002-6386","authenticated-orcid":false,"given":"Lucian","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington , Seattle, WA 98195, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-179X","authenticated-orcid":false,"given":"Matthias","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Biology, Institute of Theoretical Biology, Humboldt-University Berlin , Berlin 10115, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0156-8410","authenticated-orcid":false,"given":"Kiri","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Computational Sciences, Korea Institute for Advanced Study , Seoul 02455, Republic of Korea"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3659-6817","authenticated-orcid":false,"given":"Herbert M","family":"Sauro","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington , Seattle, WA 98195, USA"}]}],"member":"286","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"2023010805353375100_btac770-B1","first-page":"129","author":"Beazley","year":"1996"},{"key":"2023010805353375100_btac770-B2","first-page":"1637","author":"Bergmann","year":"2006"},{"key":"2023010805353375100_btac770-B3","first-page":"300","author":"Bouteiller","year":"2015"},{"key":"2023010805353375100_btac770-B4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1137\/0724031","article-title":"A local convergence theory for combined inexact-newton\/finite-difference projection methods","volume":"24","author":"Brown","year":"1987","journal-title":"SIAM J. Numer. Anal"},{"key":"2023010805353375100_btac770-B5","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/0098-1354(94)00090-B","article-title":"Sensitivity analysis of initial-boundary-value problems with mixed PDEs and algebraic equations: applications to chemical and biochemical systems","volume":"19","author":"Caracotsios","year":"1995","journal-title":"Comput. Chem. Eng"},{"key":"2023010805353375100_btac770-B6","doi-asserted-by":"crossref","first-page":"61677","DOI":"10.1109\/ACCESS.2018.2874767","article-title":"Performance analysis of google colaboratory as a tool for accelerating deep learning applications","volume":"6","author":"Carneiro","year":"2018","journal-title":"IEEE Access"},{"key":"2023010805353375100_btac770-B7","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.biosystems.2018.07.006","article-title":"Tellurium: an extensible python-based modeling environment for systems and synthetic biology","volume":"171","author":"Choi","year":"2018","journal-title":"Biosystems"},{"key":"2023010805353375100_btac770-B8","first-page":"25","article-title":"Auto: a program for the automatic bifurcation analysis of autonomous systems","volume":"30","author":"Doedel","year":"1981","journal-title":"Congr. Numer"},{"key":"2023010805353375100_btac770-B9","doi-asserted-by":"crossref","first-page":"e1005991","DOI":"10.1371\/journal.pcbi.1005991","article-title":"Physicell: an open source physics-based cell simulator for 3-d multicellular systems","volume":"14","author":"Ghaffarizadeh","year":"2018","journal-title":"PLoS Comput. Biol"},{"key":"2023010805353375100_btac770-B10","doi-asserted-by":"crossref","first-page":"e1008208","DOI":"10.1371\/journal.pcbi.1008208","article-title":"MASSpy: building, simulating, and visualizing dynamic biological models in python using mass action kinetics","volume":"17","author":"Haiman","year":"2021","journal-title":"PLoS Comput. Biol"},{"key":"2023010805353375100_btac770-B11","doi-asserted-by":"crossref","first-page":"e1002155","DOI":"10.1371\/journal.pcbi.1002155","article-title":"A multi-cell, multi-scale model of vertebrate segmentation and somite formation","volume":"7","author":"Hester","year":"2011","journal-title":"PLoS Comput. Biol"},{"key":"2023010805353375100_btac770-B12","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1145\/1089014.1089020","article-title":"SUNDIALS: suite of nonlinear and differential\/algebraic equation solvers","volume":"31","author":"Hindmarsh","year":"2005","journal-title":"ACM Transactions on Mathematical Software (TOMS)"},{"key":"2023010805353375100_btac770-B13","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1093\/bioinformatics\/btl485","article-title":"COPASI\u2014a complex pathway simulator","volume":"22","author":"Hoops","year":"2006","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B14","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/bioinformatics\/btg015","article-title":"The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models","volume":"19","author":"Hucka","year":"2003","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B15","doi-asserted-by":"crossref","DOI":"10.1515\/jib-2019-0021","article-title":"The systems biology markup language (SBML): language specification for level 3 version 2 core release 2","volume":"16","author":"Hucka","year":"2019","journal-title":"J. Integr. Bioinformatics"},{"key":"2023010805353375100_btac770-B16","first-page":"340","article-title":"Win, lose, or tie: mathematical modeling of ligand competition at the cell\u2013extracellular matrix interface","volume":"9","author":"Karag\u00f6z","year":"2021","journal-title":"Front. Bioeng. Biotechnol"},{"key":"2023010805353375100_btac770-B17","doi-asserted-by":"crossref","first-page":"e9110","DOI":"10.15252\/msb.20199110","article-title":"SBML level 3: an extensible format for the exchange and reuse of biological models","volume":"16","author":"Keating","year":"2020","journal-title":"Mol. Syst. Biol"},{"key":"2023010805353375100_btac770-B18","volume-title":"Jupyter Notebooks - A Publishing Format for Reproducible Computational Workflows","author":"Kluyver","year":"2016"},{"key":"2023010805353375100_btac770-B19","doi-asserted-by":"crossref","first-page":"757293","DOI":"10.3389\/fphys.2021.757293","article-title":"Physiologically based modeling of the effect of physiological and anthropometric variability on indocyanine green based liver function tests","volume":"12","author":"K\u00f6ller","year":"2021","journal-title":"Front. Physiol"},{"key":"2023010805353375100_btac770-B20","doi-asserted-by":"crossref","first-page":"730418","DOI":"10.3389\/fphys.2021.730418","article-title":"Prediction of survival after partial hepatectomy using a physiologically based pharmacokinetic model of indocyanine green liver function tests","volume":"12","author":"K\u00f6ller","year":"2021","journal-title":"Front. Physiol"},{"key":"2023010805353375100_btac770-B22","first-page":"75","author":"Lattner","year":"2004"},{"key":"2023010805353375100_btac770-B23","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/msb.2013.1","article-title":"Programming biological models in python using PySB","volume":"9","author":"Lopez","year":"2013","journal-title":"Mol. Syst. Biol"},{"key":"2023010805353375100_btac770-B24","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1093\/bioinformatics\/btz860","article-title":"SBML2Modelica: integrating biochemical models within open-standard simulation ecosystems","volume":"36","author":"Maggioli","year":"2020","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B25","first-page":"D407","article-title":"Biomodels\u201315 years of sharing computational models in life science","volume":"48","author":"Malik-Sheriff","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2023010805353375100_btac770-B26","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0168-9274(95)00117-4","article-title":"Numerical methods and software for sensitivity analysis of differential-algebraic systems","volume":"20","author":"Maly","year":"1996","journal-title":"Appl. Numer. Math"},{"key":"2023010805353375100_btac770-B27","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1049\/iet-syb:20080102","article-title":"Virtual cell modelling and simulation software environment","volume":"2","author":"Moraru","year":"2008","journal-title":"IET Syst. Biol"},{"key":"2023010805353375100_btac770-B28","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1093\/bioinformatics\/btp457","article-title":"iBioSim: a tool for the analysis and design of genetic circuits","volume":"25","author":"Myers","year":"2009","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B29","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1093\/bioinformatics\/btac004","article-title":"Implementation of a practical Markov chain Monte Carlo sampling algorithm in PyBioNetFit","volume":"38","author":"Neumann","year":"2022","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B30","doi-asserted-by":"crossref","first-page":"12569","DOI":"10.1038\/srep12569","article-title":"DYVIPAC: an integrated analysis and visualisation framework to probe multi-dimensional biological networks","volume":"5","author":"Nguyen","year":"2015","journal-title":"Sci. Rep"},{"key":"2023010805353375100_btac770-B31","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/bioinformatics\/bti046","article-title":"Modelling cellular systems with PySCeS","volume":"21","author":"Olivier","year":"2005","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B32","doi-asserted-by":"crossref","first-page":"100748","DOI":"10.1016\/j.isci.2019.100748","article-title":"Interactive multiresolution visualization of cellular network processes","volume":"23","author":"Ortega","year":"2020","journal-title":"iScience"},{"key":"2023010805353375100_btac770-B33","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1093\/bioinformatics\/btab669","article-title":"The systems biology simulation core library","volume":"38","author":"Panchiwala","year":"2022","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-021-04477-x","article-title":"A numerical approach for detecting switch-like bistability in mass action chemical reaction networks with conservation laws","volume":"23","author":"Reyes","year":"2022","journal-title":"BMC Bioinformatics"},{"key":"2023010805353375100_btac770-B35","volume-title":"Systems Biology: An Introduction to Pathway Modeling","author":"Sauro","year":"2014"},{"key":"2023010805353375100_btac770-B36","doi-asserted-by":"crossref","first-page":"W597","DOI":"10.1093\/nar\/gkab411","article-title":"RunBioSimulations: an extensible web application that simulates a wide range of computational modeling frameworks, algorithms, and formats","volume":"49","author":"Shaikh","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2023010805353375100_btac770-B37","author":"Shoshany","year":"2021"},{"key":"2023010805353375100_btac770-B38","author":"Smith","year":"2022"},{"key":"2023010805353375100_btac770-B39","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1093\/bioinformatics\/btp401","article-title":"Antimony: a modular model definition language","volume":"25","author":"Smith","year":"2009","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B40","doi-asserted-by":"crossref","DOI":"10.1515\/jib-2020-0018","article-title":"Systems biology markup language (SBML) level 3 package: distributions, version 1, release 1","volume":"17","author":"Smith","year":"2020","journal-title":"J. Integr. Bioinformatics"},{"key":"2023010805353375100_btac770-B41","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1093\/bioinformatics\/btv363","article-title":"libRoadRunner: a high performance SBML simulation and analysis library","volume":"31","author":"Somogyi","year":"2015","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B42","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/B978-0-12-388403-9.00013-8","article-title":"Multi-scale modeling of tissues using compucell3d","volume":"110","author":"Swat","year":"2012","journal-title":"Methods Cell Biol"},{"key":"2023010805353375100_btac770-B43","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1093\/bioinformatics\/btt157","article-title":"LibSBMLSim: a reference implementation of fully functional SBML simulator","volume":"29","author":"Takizawa","year":"2013","journal-title":"Bioinformatics"},{"key":"2023010805353375100_btac770-B44","article-title":"Dynamic flux balance analysis models in SBML","author":"Watanabe","year":"2018","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btac770\/47997871\/btac770.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/1\/btac770\/48520701\/btac770.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/1\/btac770\/48520701\/btac770.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T05:36:04Z","timestamp":1673156164000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btac770\/6883908"}},"subtitle":[],"editor":[{"given":"Pier Luigi","family":"Martelli","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btac770","relation":{},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2022,12,8]]},"article-number":"btac770"}}