Libroadrunner

libroadrunner

Initial release	March 23, 2015;10 years ago (2015-03-23)
Stable release	2.6.0 / March 26, 2024;13 months ago (2024-03-26)
Written in	Python, C++, C, FORTRAN
Operating system	Linux, macOS and Microsoft Windows
License	Apache License
Website	github.com/sys-bio/roadrunner

libRoadRunner is a C/C++ software library that supports simulation of SBML based models.. ^[1] It uses LLVM to generate extremely high-performance code and is the fastest SBML-based simulator currently available. ^[2] Its main purpose is for use as a reusable library that can be hosted by other applications, particularly on large compute clusters for doing parameter optimization where performance is critical. It also has a set of Python bindings that allow it to be easily used from Python as well as a set of bindings for Julia. ^[3]

libroadrunner is often paired with Tellurium, ^[4] which adds additional functionality such as Antimony ^[5] scripting.

Capabilities

• Time-course simulation using the CVODE, RK45, and Euler solvers of ordinary differential equations, which can report on the system's variable concentrations and reaction rates over time.

• Steady-state calculations using non-linear solvers such as kinsolve ^[6] and NLEQ2 ^[7]

• Stochastic simulation using the standard Gillespie algorithm.

• Supports both steady-state and time-dependent Metabolic control analysis, including calculating the elasticities towards the variable metabolites by algebraic or numerical differentiation of the rate equations, as well as the flux and concentration control coefficients by means of matrix inversion ^[8] and perturbation methods. ^[9]

• libroadrunner will also compute the structural matrices (e.g. K- and L-matrices) of a stoichiometric model. ^[10]

• The stability of a system can be investigated by way of the system eigenvalues.

• Data and results can be plotted via matplotlib, or saved in text files.

• libroadrunner supports the import and export of standard SBML.

Applications

libroadrunner has been widely used in the systems biology community for doing research in systems biology modeling, as well as being a host for other simulation platforms.

Software applications that use libroadrunner

• CompuCell3D
• CRNT4SBML ^[11]
• DIVIPAC ^[12]
• massPy ^[13]
• pyBioNetFit ^[14]
• PhysiCell ^[15]
• pyViPR ^[16]
• runBiosimulations ^[17]
• SBMLSim ^[18]
• Tellurium (simulation tool) ^[19]
• Tissue Forge (multi-cellular simulator) ^[20]
• TOPAS-Tissue ^[21]

Research applications

libroadrunner has been used in a large variety of research projects. The following lists a small number of those studies:

• Tickman et al, ^[22] describe developing multi-layer CRIPRa/i circuits for genetic programs using Tellurium/libroadrunner as the computational application.

• Salazar-Cavazos et al ^[23] used pyBioNetFit/libroadrunner to investigate Multisite EGFR phosphorylation.

• Douilhet et al. ^[24] used Tellurium/libroadrunner to investigate the use of genetic algorithms with rank selection optimization.

• Schmiester et al. ^[25] used pyBioNetFit/libroadrunner to investigate gradient-based parameter estimation using qualitative data.

• Yang et al ^[26] used CompuCell3D/libroadrunner to model transcript factor cooperation in mouse liver.

Notability

• libroadrunner was the first SBML simulation to use just-in-time compilation using LLVM.
• It is the only SBML simulator that exploits AUTO2000 for bifurcation analysis. ^[27]

A number of reviews and commentaries have been written that discuss libroadrunner:

• Maggioli et al. ^[28] conduct a speed comparison of various SBML simulators and conclude libroadrunner is the fastest SBML simulator currently available to researchers.

• Koster et al, ^[29] discuss the speed advantages of libroadrunner for solving differential equations compared to solving stochastic systems.

Development

Development of libroadrunner is primarily funded through research grants from the National Institutes of Health ^[30]

See also

• List of systems biology modeling software

References

1. Somogyi, Endre T.; Bouteiller, Jean-Marie; Glazier, James A.; König, Matthias; Medley, J. Kyle; Swat, Maciej H.; Sauro, Herbert M. (15 October 2015). "libRoadRunner: a high performance SBML simulation and analysis library: Table 1". Bioinformatics. 31 (20): 3315–3321. doi:10.1093/bioinformatics/btv363. PMC   4607739 . PMID   26085503.
2. Maggioli, F; Mancini, T; Tronci, E (1 April 2020). "SBML2Modelica: integrating biochemical models within open-standard simulation ecosystems". Bioinformatics. 36 (7): 2165–2172. arXiv: 2106.02609 . doi:10.1093/bioinformatics/btz860. PMID   31738386.
3. Welsh, Ciaran; Xu, Jin; Smith, Lucian; König, Matthias; Choi, Kiri; Sauro, Herbert M (1 January 2023). "libRoadRunner 2.0: a high performance SBML simulation and analysis library". Bioinformatics. 39 (1). arXiv: 1503.01095 . doi:10.1093/bioinformatics/btac770. PMC   9825722 . PMID   36478036.
4. Choi, Kiri; Medley, J. Kyle; König, Matthias; Stocking, Kaylene; Smith, Lucian; Gu, Stanley; Sauro, Herbert M. (September 2018). "Tellurium: An extensible python-based modeling environment for systems and synthetic biology". Biosystems. 171: 74–79. Bibcode:2018BiSys.171...74C. doi:10.1016/j.biosystems.2018.07.006. PMC   6108935 . PMID   30053414.
5. Smith, L. P.; Bergmann, F. T.; Chandran, D.; Sauro, H. M. (15 September 2009). "Antimony: a modular model definition language". Bioinformatics. 25 (18): 2452–2454. doi:10.1093/bioinformatics/btp401. PMC   2735663 . PMID   19578039.
6. Hindmarsh, Alan C.; Brown, Peter N.; Grant, Keith E.; Lee, Steven L.; Serban, Radu; Shumaker, Dan E.; Woodward, Carol S. (September 2005). "SUNDIALS: Suite of nonlinear and differential/algebraic equation solvers". ACM Transactions on Mathematical Software. 31 (3): 363–396. doi:10.1145/1089014.1089020. OSTI   15002968. S2CID   6826941.
7. Deuflhard, P (2004). Newton Methods for Nonlinear Problems. Springer-Verlag, NY.
8. Hofmeyr, Jannie (2001). "Metabolic control analysis in a nutshell". Proceedings of the 2nd International Conference on Systems Biology. S2CID   17007756.
9. Yip, Evan; Sauro, Herbert (2021). "Computing Sensitivities in Reaction Networks using Finite Difference Methods". arXiv: 2110.04335 .{{cite journal}}: Cite journal requires |journal= (help)
10. Kerkhoven, Eduard J.; Achcar, Fiona; Alibu, Vincent P.; Burchmore, Richard J.; Gilbert, Ian H.; Trybiło, Maciej; Driessen, Nicole N.; Gilbert, David; Breitling, Rainer; Bakker, Barbara M.; Barrett, Michael P. (5 December 2013). "Handling Uncertainty in Dynamic Models: The Pentose Phosphate Pathway in Trypanosoma brucei". PLOS Computational Biology. 9 (12): e1003371. Bibcode:2013PLSCB...9E3371K. doi: 10.1371/journal.pcbi.1003371 . PMC   3854711 . PMID   24339766.
11. Reyes, Brandon C; Otero-Muras, Irene; Shuen, Michael T; Tartakovsky, Alexandre M; Petyuk, Vladislav A (1 June 2020). "CRNT4SBML: a Python package for the detection of bistability in biochemical reaction networks". Bioinformatics. 36 (12): 3922–3924. doi: 10.1093/bioinformatics/btaa241 . PMID   32289149.
12. Nguyen, Lan K.; Degasperi, Andrea; Cotter, Philip; Kholodenko, Boris N. (December 2015). "DYVIPAC: an integrated analysis and visualisation framework to probe multi-dimensional biological networks". Scientific Reports. 5 (1): 12569. Bibcode:2015NatSR...512569N. doi:10.1038/srep12569. PMC   4518224 . PMID   26220783.
13. Haiman, Zachary B.; Zielinski, Daniel C.; Koike, Yuko; Yurkovich, James T.; Palsson, Bernhard O. (28 January 2021). "MASSpy: Building, simulating, and visualizing dynamic biological models in Python using mass action kinetics". PLOS Computational Biology. 17 (1): e1008208. Bibcode:2021PLSCB..17E8208H. doi: 10.1371/journal.pcbi.1008208 . PMC   7872247 . PMID   33507922.
14. Neumann, Jacob; Lin, Yen Ting; Mallela, Abhishek; Miller, Ely F; Colvin, Joshua; Duprat, Abell T; Chen, Ye; Hlavacek, William S; Posner, Richard G (4 March 2022). "Implementation of a practical Markov chain Monte Carlo sampling algorithm in PyBioNetFit". Bioinformatics. 38 (6): 1770–1772. doi:10.1093/bioinformatics/btac004. PMC   10060707 . PMID   34986226.
15. Ghaffarizadeh, Ahmadreza; Heiland, Randy; Friedman, Samuel H.; Mumenthaler, Shannon M.; Macklin, Paul (23 February 2018). "PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems". PLOS Computational Biology. 14 (2): e1005991. Bibcode:2018PLSCB..14E5991G. doi: 10.1371/journal.pcbi.1005991 . PMC   5841829 . PMID   29474446.
16. Ortega, Oscar O.; Lopez, Carlos F. (January 2020). "Interactive Multiresolution Visualization of Cellular Network Processes". iScience. 23 (1): 100748. Bibcode:2020iSci...23j0748O. doi:10.1016/j.isci.2019.100748. PMC   6941861 . PMID   31884165.
17. Shaikh, Bilal; Marupilla, Gnaneswara; Wilson, Mike; Blinov, Michael L; Moraru, Ion; Karr, Jonathan R (2 July 2021). "RunBioSimulations: an extensible web application that simulates a wide range of computational modeling frameworks, algorithms, and formats". Nucleic Acids Research. 49 (W1): W597 –W602. doi:10.1093/nar/gkab411. PMC   8262693 . PMID   34019658.
18. Konig, Matthias. "SBMLSim". GitHub .
19. Choi, Kiri; Medley, J. Kyle; König, Matthias; Stocking, Kaylene; Smith, Lucian; Gu, Stanley; Sauro, Herbert M. (September 2018). "Tellurium: An extensible python-based modeling environment for systems and synthetic biology". Biosystems. 171: 74–79. Bibcode:2018BiSys.171...74C. doi:10.1016/j.biosystems.2018.07.006. PMC   6108935 . PMID   30053414.
20. Sego, T. J.; Sluka, James P.; Sauro, Herbert M.; Glazier, James A. (23 October 2023). "Tissue Forge: Interactive biological and biophysics simulation environment". PLOS Computational Biology. 19 (10): e1010768. Bibcode:2023PLSCB..19E0768S. doi: 10.1371/journal.pcbi.1010768 . PMC   10621971 . PMID   37871133.
21. García García, Omar Rodrigo; Ortiz, Ramon; Moreno-Barbosa, Eduardo; D-Kondo, Naoki; Faddegon, Bruce; Ramos-Méndez, Jose (19 September 2024). "TOPAS-Tissue: A Framework for the Simulation of the Biological Response to Ionizing Radiation at the Multi-Cellular Level". International Journal of Molecular Sciences. 25 (18): 10061. doi: 10.3390/ijms251810061 . PMC   11431975 . PMID   39337547.
22. Tickman, Benjamin I.; Burbano, Diego Alba; Chavali, Venkata P.; Kiattisewee, Cholpisit; Fontana, Jason; Khakimzhan, Aset; Noireaux, Vincent; Zalatan, Jesse G.; Carothers, James M. (March 2022). "Multi-layer CRISPRa/i circuits for dynamic genetic programs in cell-free and bacterial systems". Cell Systems. 13 (3): 215–229.e8. doi: 10.1016/j.cels.2021.10.008 . PMID   34800362. S2CID   244430298.
23. Salazar-Cavazos, Emanuel; Nitta, Carolina Franco; Mitra, Eshan D.; Wilson, Bridget S.; Lidke, Keith A.; Hlavacek, William S.; Lidke, Diane S. (19 March 2020). "Multisite EGFR phosphorylation is regulated by adaptor protein abundances and dimer lifetimes". Molecular Biology of the Cell. 31 (7): 695–708. doi:10.1091/mbc.E19-09-0548. PMC   7202077 . PMID   31913761. S2CID   210119415.
24. Douilhet, Gemma; Niranjan, Mahesan; Vallejo, Andres; Clayton, Kalum; Davies, James; Sirvent, Sofia; Pople, Jenny; Ardern-Jones, Michael R; Polak, Marta E (23 February 2022). "Genetic Algorithm with Rank Selection optimises robust parameter estimation for systems biology models". bioRxiv   10.1101/2022.02.22.481394 .
25. Schmiester, Leonard; Weindl, Daniel; Hasenauer, Jan (7 December 2021). "Efficient gradient-based parameter estimation for dynamic models using qualitative data". Bioinformatics. 37 (23): 4493–4500. doi:10.1093/bioinformatics/btab512. PMC   8652033 . PMID   34260697.
26. Yang, Yongliang; Filipovic, David; Bhattacharya, Sudin (April 2022). "A Negative Feedback Loop and Transcription Factor Cooperation Regulate Zonal Gene Induction by 2, 3, 7, 8-Tetrachlorodibenzo-p-Dioxin in the Mouse Liver". Hepatology Communications. 6 (4): 750–764. doi:10.1002/hep4.1848. PMC   8948569 . PMID   34726355. S2CID   240422386.
27. "Bifurcation Analysis".
28. Maggioli, F; Mancini, T; Tronci, E (1 April 2020). "SBML2Modelica: integrating biochemical models within open-standard simulation ecosystems". Bioinformatics. 36 (7): 2165–2172. arXiv: 2106.02609 . doi:10.1093/bioinformatics/btz860. PMID   31738386.
29. Köster, Till; Warnke, Tom; Uhrmacher, Adelinde M. (30 April 2022). "Generating Fast Specialized Simulators for Stochastic Reaction Networks via Partial Evaluation". ACM Transactions on Modeling and Computer Simulation. 32 (2): 1–25. doi:10.1145/3485465. S2CID   247273613.
30. Sauro, Herbert. "Development Support".

External links

• GitHub page