SBML Level 3: an extensible format for the exchange and reuse of biological models

Sarah M. Keating; Dagmar Waltemath; Matthias König; Fengkai Zhang; Andreas Dräger; Claudine Chaouiya; Frank T. Bergmann; Andrew Finney; Colin S. Gillespie; Tomáš Helikar; Stefan Hoops; Rahuman S. Malik-Sheriff; Stuart L. Moodie; Ion I. Moraru; Chris J. Myers; Aurélien Naldi; Brett G. Olivier; Sven Sahle; James C. Schaff; Lucian P. Smith; Maciej J. Swat; Denis Thieffry; Leandro Watanabe; Darren J. Wilkinson; Michael L. Blinov; Kimberly Begley; James R. Faeder; Harold F. Gómez; Thomas M. Hamm; Yuichiro Inagaki; Wolfram Liebermeister; Allyson L. Lister; Daniel Lucio; Eric Mjolsness; Carole J. Proctor; Karthik Raman; Nicolas Rodriguez; Clifford A. Shaffer; Bruce E. Shapiro; Joerg Stelling; Neil Swainston; Naoki Tanimura; John Wagner; Martin Meier-Schellersheim; Herbert M. Sauro; Bernhard Palsson; Hamid Bolouri; Hiroaki Kitano; Akira Funahashi; Henning Hermjakob; John C. Doyle; Michael Hucka; Richard R. Adams; Nicholas A. Allen; Bastian R. Angermann; Marco Antoniotti; Gary D. Bader; Jan Červený; Mélanie Courtot; Chris D. Cox; Piero Dalle Pezze; Emek Demir; William S. Denney; Harish Dharuri; Julien Dorier; Dirk Drasdo; Ali Ebrahim; Johannes Eichner; Johan Elf; Lukas Endler; Chris T. Evelo; Christoph Flamm; Ronan M.T. Fleming; Martina Fröhlich; Mihai Glont; Emanuel Gonçalves; Martin Golebiewski; Hovakim Grabski; Alex Gutteridge; Damon Hachmeister; Leonard A. Harris; Benjamin D. Heavner; Ron Henkel; William S. Hlavacek; Bin Hu; Daniel R. Hyduke; Hidde de Jong; Nick Juty; Peter D. Karp; Jonathan R. Karr; Douglas B. Kell; Roland Keller; Ilya Kiselev; Steffen Klamt; Edda Klipp; Christian Knüpfer; Fedor Kolpakov; Falko Krause; Martina Kutmon; Camille Laibe; Conor Lawless; Lu Li; Leslie M. Loew; Rainer Machne; Yukiko Matsuoka; Pedro Mendes; Huaiyu Mi; Florian Mittag; Pedro T. Monteiro; Kedar Nath Natarajan; Poul M.F. Nielsen; Tramy Nguyen; Alida Palmisano; Jean Baptiste Pettit; Thomas Pfau; Robert D. Phair; Tomas Radivoyevitch; Johann M. Rohwer; Oliver A. Ruebenacker; Julio Saez-Rodriguez; Martin Scharm; Henning Schmidt; Falk Schreiber; Michael Schubert; Roman Schulte; Stuart C. Sealfon; Kieran Smallbone; Sylvain Soliman; Melanie I. Stefan; Devin P. Sullivan; Koichi Takahashi; Bas Teusink; David Tolnay; Ibrahim Vazirabad; Axel von Kamp; Ulrike Wittig; Clemens Wrzodek; Finja Wrzodek; Ioannis Xenarios; Anna Zhukova; Jeremy Zucker

doi:10.15252/msb.20199110

SBML Level 3: an extensible format for the exchange and reuse of biological models

Sarah M. Keating, Dagmar Waltemath, Matthias König, Fengkai Zhang, Andreas Dräger, Claudine Chaouiya, Frank T. Bergmann, Andrew Finney, Colin S. Gillespie, Tomáš Helikar, Stefan Hoops, Rahuman S. Malik-Sheriff, Stuart L. Moodie, Ion I. Moraru, Chris J. Myers, Aurélien Naldi, Brett G. Olivier, Sven Sahle, James C. Schaff, Lucian P. SmithMaciej J. Swat, Denis Thieffry, Leandro Watanabe, Darren J. Wilkinson, Michael L. Blinov, Kimberly Begley, James R. Faeder, Harold F. Gómez, Thomas M. Hamm, Yuichiro Inagaki, Wolfram Liebermeister, Allyson L. Lister, Daniel Lucio, Eric Mjolsness, Carole J. Proctor, Karthik Raman, Nicolas Rodriguez, Clifford A. Shaffer, Bruce E. Shapiro, Joerg Stelling, Neil Swainston, Naoki Tanimura, John Wagner, Martin Meier-Schellersheim, Herbert M. Sauro, Bernhard Palsson, Hamid Bolouri, Hiroaki Kitano, Akira Funahashi, Henning Hermjakob, John C. Doyle, Michael Hucka, Richard R. Adams, Nicholas A. Allen, Bastian R. Angermann, Marco Antoniotti, Gary D. Bader, Jan Červený, Mélanie Courtot, Chris D. Cox, Piero Dalle Pezze, Emek Demir, William S. Denney, Harish Dharuri, Julien Dorier, Dirk Drasdo, Ali Ebrahim, Johannes Eichner, Johan Elf, Lukas Endler, Chris T. Evelo, Christoph Flamm, Ronan M.T. Fleming, Martina Fröhlich, Mihai Glont, Emanuel Gonçalves, Martin Golebiewski, Hovakim Grabski, Alex Gutteridge, Damon Hachmeister, Leonard A. Harris, Benjamin D. Heavner, Ron Henkel, William S. Hlavacek, Bin Hu, Daniel R. Hyduke, Hidde de Jong, Nick Juty, Peter D. Karp, Jonathan R. Karr, Douglas B. Kell, Roland Keller, Ilya Kiselev, Steffen Klamt, Edda Klipp, Christian Knüpfer, Fedor Kolpakov, Falko Krause, Martina Kutmon, Camille Laibe, Conor Lawless, Lu Li, Leslie M. Loew, Rainer Machne, Yukiko Matsuoka, Pedro Mendes, Huaiyu Mi, Florian Mittag, Pedro T. Monteiro, Kedar Nath Natarajan, Poul M.F. Nielsen, Tramy Nguyen, Alida Palmisano, Jean Baptiste Pettit, Thomas Pfau, Robert D. Phair, Tomas Radivoyevitch, Johann M. Rohwer, Oliver A. Ruebenacker, Julio Saez-Rodriguez, Martin Scharm, Henning Schmidt, Falk Schreiber, Michael Schubert, Roman Schulte, Stuart C. Sealfon, Kieran Smallbone, Sylvain Soliman, Melanie I. Stefan, Devin P. Sullivan, Koichi Takahashi, Bas Teusink, David Tolnay, Ibrahim Vazirabad, Axel von Kamp, Ulrike Wittig, Clemens Wrzodek, Finja Wrzodek, Ioannis Xenarios, Anna Zhukova, Jeremy Zucker

Department of Biosciences and Informatics

Research output: Contribution to journal › Review article › peer-review

64 Citations (Scopus)

Abstract

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.

Original language	English
Article number	e9110
Journal	Molecular systems biology
Volume	16
Issue number	8
DOIs	https://doi.org/10.15252/msb.20199110
Publication status	Published - 2020 Aug 1

Keywords

computational modeling
file format
interoperability
reproducibility
systems biology

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)
Agricultural and Biological Sciences(all)
Applied Mathematics

Access to Document

10.15252/msb.20199110

Cite this

Keating, S. M., Waltemath, D., König, M., Zhang, F., Dräger, A., Chaouiya, C., Bergmann, F. T., Finney, A., Gillespie, C. S., Helikar, T., Hoops, S., Malik-Sheriff, R. S., Moodie, S. L., Moraru, I. I., Myers, C. J., Naldi, A., Olivier, B. G., Sahle, S., Schaff, J. C., ... Zucker, J. (2020). SBML Level 3: an extensible format for the exchange and reuse of biological models. Molecular systems biology, 16(8), [e9110]. https://doi.org/10.15252/msb.20199110

Keating, SM, Waltemath, D, König, M, Zhang, F, Dräger, A, Chaouiya, C, Bergmann, FT, Finney, A, Gillespie, CS, Helikar, T, Hoops, S, Malik-Sheriff, RS, Moodie, SL, Moraru, II, Myers, CJ, Naldi, A, Olivier, BG, Sahle, S, Schaff, JC, Smith, LP, Swat, MJ, Thieffry, D, Watanabe, L, Wilkinson, DJ, Blinov, ML, Begley, K, Faeder, JR, Gómez, HF, Hamm, TM, Inagaki, Y, Liebermeister, W, Lister, AL, Lucio, D, Mjolsness, E, Proctor, CJ, Raman, K, Rodriguez, N, Shaffer, CA, Shapiro, BE, Stelling, J, Swainston, N, Tanimura, N, Wagner, J, Meier-Schellersheim, M, Sauro, HM, Palsson, B, Bolouri, H, Kitano, H, Funahashi, A, Hermjakob, H, Doyle, JC, Hucka, M, Adams, RR, Allen, NA, Angermann, BR, Antoniotti, M, Bader, GD, Červený, J, Courtot, M, Cox, CD, Dalle Pezze, P, Demir, E, Denney, WS, Dharuri, H, Dorier, J, Drasdo, D, Ebrahim, A, Eichner, J, Elf, J, Endler, L, Evelo, CT, Flamm, C, Fleming, RMT, Fröhlich, M, Glont, M, Gonçalves, E, Golebiewski, M, Grabski, H, Gutteridge, A, Hachmeister, D, Harris, LA, Heavner, BD, Henkel, R, Hlavacek, WS, Hu, B, Hyduke, DR, de Jong, H, Juty, N, Karp, PD, Karr, JR, Kell, DB, Keller, R, Kiselev, I, Klamt, S, Klipp, E, Knüpfer, C, Kolpakov, F, Krause, F, Kutmon, M, Laibe, C, Lawless, C, Li, L, Loew, LM, Machne, R, Matsuoka, Y, Mendes, P, Mi, H, Mittag, F, Monteiro, PT, Natarajan, KN, Nielsen, PMF, Nguyen, T, Palmisano, A, Pettit, JB, Pfau, T, Phair, RD, Radivoyevitch, T, Rohwer, JM, Ruebenacker, OA, Saez-Rodriguez, J, Scharm, M, Schmidt, H, Schreiber, F, Schubert, M, Schulte, R, Sealfon, SC, Smallbone, K, Soliman, S, Stefan, MI, Sullivan, DP, Takahashi, K, Teusink, B, Tolnay, D, Vazirabad, I, von Kamp, A, Wittig, U, Wrzodek, C, Wrzodek, F, Xenarios, I, Zhukova, A & Zucker, J 2020, 'SBML Level 3: an extensible format for the exchange and reuse of biological models', Molecular systems biology, vol. 16, no. 8, e9110. https://doi.org/10.15252/msb.20199110

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title = "SBML Level 3: an extensible format for the exchange and reuse of biological models",

abstract = "Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.",

keywords = "computational modeling, file format, interoperability, reproducibility, systems biology",

author = "Keating, {Sarah M.} and Dagmar Waltemath and Matthias K{\"o}nig and Fengkai Zhang and Andreas Dr{\"a}ger and Claudine Chaouiya and Bergmann, {Frank T.} and Andrew Finney and Gillespie, {Colin S.} and Tom{\'a}{\v s} Helikar and Stefan Hoops and Malik-Sheriff, {Rahuman S.} and Moodie, {Stuart L.} and Moraru, {Ion I.} and Myers, {Chris J.} and Aur{\'e}lien Naldi and Olivier, {Brett G.} and Sven Sahle and Schaff, {James C.} and Smith, {Lucian P.} and Swat, {Maciej J.} and Denis Thieffry and Leandro Watanabe and Wilkinson, {Darren J.} and Blinov, {Michael L.} and Kimberly Begley and Faeder, {James R.} and G{\'o}mez, {Harold F.} and Hamm, {Thomas M.} and Yuichiro Inagaki and Wolfram Liebermeister and Lister, {Allyson L.} and Daniel Lucio and Eric Mjolsness and Proctor, {Carole J.} and Karthik Raman and Nicolas Rodriguez and Shaffer, {Clifford A.} and Shapiro, {Bruce E.} and Joerg Stelling and Neil Swainston and Naoki Tanimura and John Wagner and Martin Meier-Schellersheim and Sauro, {Herbert M.} and Bernhard Palsson and Hamid Bolouri and Hiroaki Kitano and Akira Funahashi and Henning Hermjakob and Doyle, {John C.} and Michael Hucka and Adams, {Richard R.} and Allen, {Nicholas A.} and Angermann, {Bastian R.} and Marco Antoniotti and Bader, {Gary D.} and Jan {\v C}erven{\'y} and M{\'e}lanie Courtot and Cox, {Chris D.} and {Dalle Pezze}, Piero and Emek Demir and Denney, {William S.} and Harish Dharuri and Julien Dorier and Dirk Drasdo and Ali Ebrahim and Johannes Eichner and Johan Elf and Lukas Endler and Evelo, {Chris T.} and Christoph Flamm and Fleming, {Ronan M.T.} and Martina Fr{\"o}hlich and Mihai Glont and Emanuel Gon{\c c}alves and Martin Golebiewski and Hovakim Grabski and Alex Gutteridge and Damon Hachmeister and Harris, {Leonard A.} and Heavner, {Benjamin D.} and Ron Henkel and Hlavacek, {William S.} and Bin Hu and Hyduke, {Daniel R.} and {de Jong}, Hidde and Nick Juty and Karp, {Peter D.} and Karr, {Jonathan R.} and Kell, {Douglas B.} and Roland Keller and Ilya Kiselev and Steffen Klamt and Edda Klipp and Christian Kn{\"u}pfer and Fedor Kolpakov and Falko Krause and Martina Kutmon and Camille Laibe and Conor Lawless and Lu Li and Loew, {Leslie M.} and Rainer Machne and Yukiko Matsuoka and Pedro Mendes and Huaiyu Mi and Florian Mittag and Monteiro, {Pedro T.} and Natarajan, {Kedar Nath} and Nielsen, {Poul M.F.} and Tramy Nguyen and Alida Palmisano and Pettit, {Jean Baptiste} and Thomas Pfau and Phair, {Robert D.} and Tomas Radivoyevitch and Rohwer, {Johann M.} and Ruebenacker, {Oliver A.} and Julio Saez-Rodriguez and Martin Scharm and Henning Schmidt and Falk Schreiber and Michael Schubert and Roman Schulte and Sealfon, {Stuart C.} and Kieran Smallbone and Sylvain Soliman and Stefan, {Melanie I.} and Sullivan, {Devin P.} and Koichi Takahashi and Bas Teusink and David Tolnay and Ibrahim Vazirabad and {von Kamp}, Axel and Ulrike Wittig and Clemens Wrzodek and Finja Wrzodek and Ioannis Xenarios and Anna Zhukova and Jeremy Zucker",

note = "Funding Information: A.G. was supported by the Japanese Society for the Promotion of Science. Funding Information: D.K. was supported by Novo Nordisk Foundation grant NNF10CC1016517. Funding Information: M.G. was supported by funding to HITS from the German Federal Ministry of Education and Research (BMBF) as part of the Liver Systems Medicine Network LiSyM (FKZ 031L0056) and through the MulticellML project (FKZ 01ZX1707B), as well as from the European Union Horizon2020 framework programme of the European Commission under Grant Agreement 825843 and from the Klaus Tschira Foundation (KTS). Funding Information: D.D. was supported by grant iLite (Innovations for LIver and Tissue Engineering) from Agence nationale de la recherche (ANR, France) to INRIA, Paris, France; by grant LiSyM (Liver Systems Medicine) from Bundesministerium f{\"u}r Bildung und Forschung (BMBF, Germany) to IfADo, Dortmund, Germany; by grant VLN (Virtual Liver Network) from Bundesministerium f{\"u}r Bildung und Forschung (BMBF, Germany) to IfADo, Dortmund, Germany; by grant Physicancer from Institut national de la sant{\'e} et de la recherche m{\'e}dicale (INSERM, France) to INRIA, Paris, France; and by grant NOTOX (Predicting long‐term toxic effects using computer models based on systems characterisations of organotypic cultures) from EU 7 Framework Programme to INRIA, Paris, France. th Funding Information: L.M.L. was supported by grant P41‐GM103313 from the NIH (US) to the University of Connecticut School of Medicine. Funding Information: M.L.B. was supported by grant P41‐GM103313 and R01‐GM095485 from the NIH (US) to the University of Connecticut School of Medicine. Funding Information: E.K. was supported by Deutsche Forschungsgemeinschaft (DFG, GRK1772, GRK 2290 and TRR175) and by People Programme (Marie Sk{\l}odowska‐Curie Actions H2020‐MSCA‐ITN‐2015‐675585). Funding Information: B.A.'s work on SBML Level 3 was supported by the National Institutes of Health (NIH, US) and he is currently employed by AstraZeneca. Funding Information: F.K. was supported by the Russian Foundation for Basic Research, 17‐00‐00296, Institute of Computational Technologies of SB RAS, Novosibirsk, 630090, Russian Federation (PI: Fedor Kolpakov). Funding Information: W.S.H. was supported by grant R01‐GM111510 from the National Institute of General Medical Sciences (NIGMS, US) of the NIH. Funding Information: C.E. was supported by CHARME, COST, Action CA15110 MoU (PI: Chris Evelo) to Maastricht University. Funding Information: We sincerely thank all current and past SBML users, developers, contributors, supporters, advisors, administrators, and community members. We give special thanks to the following people for contributions and support: Jim Anderson, Nadia Anwar, Gordon Ball, Duncan B?renguier, Upinder Bhalla, Fr?d?ric Y. Bois, Benjamin Bornstein, Richard Boys, Ann Chasson, Thomas Cokelaer, Marco Donizelli, Alexander D?rr, Marine Dumousseau (Sivade), Lisa Falk, David Fange, Ed Frank, Ralph Gauges, Martin Ginkel, Nail Gizzatkulov, Victoria Gor, Igor Goryanin, Ryan N. Gutenkunst, Arnaud Henry, Stefanie Hoffmann, Duncan Hull, Dagmar Iber, Gael Jalowicki, Henrik Johansson, Akiya Jouraku, Devesh Khandelwal, Thomas B. L. Kirkwood, Victor Kofia, Benjamin L. Kovitz, Bryan Kowal, Andreas Kremling, Ursula Kummer, Hiroyuki Kuwahara, Anuradha Lakshminarayana, Nicolas Le Nov?re, Thomas S. Ligon, Adrian Lopez, Timo Lubitz, Peter Lyster, Natalia Maltsev, Jakob Matthes, Joanne Matthews, Tommaso Mazza, Eric Minch, Sebastian Nagel, Maki Nakayama, Poul M. F. Nielsen, German Nudelman, Anika Oellrich, Nobuyuki Ohta, Michel Page, Victoria Petri, Ranjit Randhawa, Veerasamy Ravichandran, Elisabeth Remy, Isabel Rojas, Ursula Rost, Jan D. Rudolph, Takayuki Saito, Takeshi Sakurada, Howard Salis, Maria J. Schilstra, Marvin Schulz, Shalin Shah, Daryl Shanley, Tom Shimizu, Jacky Snoep, Hugh D. Spence, Yves Sucaet, Linda Taddeo, Jose Juan Tapia, Alex Thomas, Jannis Uhlendorf, Martijn P. van Iersel, Marc Vass, Jonathan Webb, Katja Wengler, Benjamin Wicks, Sarala Wimalaratne, Haoran Yu, Thomas J. Zajac, W. Jim Zheng, and Jason Zwolak. The principal authors thank many funding agencies for their support of this work. F.B., A.D., M.H., T.M.H., S.M.K., B.O., and L.S., as well as SBML.org and its online resources, were supported by the National Institute of General Medical Sciences (NIGMS, US), grant R01-GM070923 (PI: Hucka). In addition, F.B. has been supported by the Bundesministerium f?r Bildung und Forschung (BMBF, DE), grant de.NBI ModSim1, 031L0104A (PI: Ursula Kummer). M.L.B. has been supported by NIH (US) grant P41-GM103313 and R01-GM095485. A.D. has been supported by infrastructural funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, and by the German Center for Infection Research (DZIF). A.F. was supported by the Grant-in-Aid for Young Scientists (B), grant 21700328 from JSPS KAKENHI (JP) to Keio University. J.F. was supported by National Institutes of Health (NIH, US) grant P41-GM103712 to the National Center for Multiscale Modeling of Biological Systems (MMBioS). H.H. was supported by the Biotechnology and Biological Sciences Research Council (BBSRC, UK) ?MultiMod? project (grant BB/N019482/1). T.H. was supported by NIH (US) grant 5R35-GM119770-03 to the University of Nebraska?Lincoln. S.H. was supported by NIGMS (US) grant R01-GM080219. M.K. was supported by the Federal Ministry of Education and Research (BMBF, DE), research network Systems Medicine of the Liver (LiSyM), grant 031L0054, Humboldt-University Berlin (PI: K?nig). A.L. was supported by the BBSRC (UK) while working at the Centre for Integrated Systems Biology of Ageing and Nutrition (CISBAN), Newcastle University. C.M. was supported by the National Science Foundation (NSF, USA) under grant CCF-1748200 and CCF-1856740. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF. I.M. was supported by NIH grant P41-EB023912 and P41-GM103313. K.R. was supported by the Department of Biotechnology, Government of India (grant BT/PR4949/BRB/10/1048/2012). M.M.-S. was supported by the Intramural Research Program of NIAID, NIH (US). R.M.-S. was supported by the BBSRC (UK) ?MultiMod? project (grant BB/N019482/1). B.P.'s was supported by NIH (US) grant GM57089 to the University of California, San Diego, and by the Novo Nordisk Foundation Grant NNF10CC1016517. H.M.S. was supported by NIGMS (US) grant R01-GM123032 (PI: Sauro) and by the National Institute of Biomedical Imaging and Bioengineering (NIBIB, US) grant P41-EB023912 (PI: Sauro). J.C.S. was supported by NIGMS (US) grant P41-GM103313. M.S. was supported by the DDMoRe program (EU), Innovative Medicines Initiative Joint Undertaking under grant agreement 115156. N.S. was supported by BBSRC (UK) grant ?Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM) ?, grant BB/M017702/1 (PI: Nigel S. Scrutton). F.Z. was supported by the Intramural Research Program of NIAID, NIH (US). We also thank the Google Summer of Code program for support of SBML software development. B.A.'s work on SBML Level 3 was supported by the National Institutes of Health (NIH, US) and he is currently employed by AstraZeneca. G.B. was supported by National Resource for Network Biology (NRNB, US), award 5P41-GM103504. M.L.B. was supported by grant P41-GM103313 and R01-GM095485 from the NIH (US) to the University of Connecticut School of Medicine. J.?. was supported by the Czech Research Infrastructure Infrastructure for Systems Biology C4SYS, project LM2015055; GA ?R, grant 18-24397S; and the MEYS of the Czech Republic under OP RDE grant CZ.02.1.01/0.0/0.0/16_026/0008413 ?Strategic Partnership for Environmental Technologies and Energy Production?. D.D. was supported by grant iLite (Innovations for LIver and Tissue Engineering) from Agence nationale de la recherche (ANR, France) to INRIA, Paris, France; by grant LiSyM (Liver Systems Medicine) from Bundesministerium f?r Bildung und Forschung (BMBF, Germany) to IfADo, Dortmund, Germany; by grant VLN (Virtual Liver Network) from Bundesministerium f?r Bildung und Forschung (BMBF, Germany) to IfADo, Dortmund, Germany; by grant Physicancer from Institut national de la sant? et de la recherche m?dicale (INSERM, France) to INRIA, Paris, France; and by grant NOTOX (Predicting long-term toxic effects using computer models based on systems characterisations of organotypic cultures) from EU 7th Framework Programme to INRIA, Paris, France. C.E. was supported by CHARME, COST, Action CA15110 MoU (PI: Chris Evelo) to Maastricht University. R.F. was supported by the U.S. Department of Energy, Offices of Advanced Scientific Computing Research and the Biological and Environmental Research as part of the Scientific Discovery Through Advanced Computing program, grant DE-SC0010429. A.G. was supported by the Japanese Society for the Promotion of Science. M.G. was supported by funding to HITS from the German Federal Ministry of Education and Research (BMBF) as part of the Liver Systems Medicine Network LiSyM (FKZ 031L0056) and through the MulticellML project (FKZ 01ZX1707B), as well as from the European Union Horizon2020 framework programme of the European Commission under Grant Agreement 825843 and from the Klaus Tschira Foundation (KTS). M.G.G. was supported by European Molecular Biology Laboratory (EMBL) core funding. W.S.H. was supported by grant R01-GM111510 from the National Institute of General Medical Sciences (NIGMS, US) of the NIH. D.K. was supported by Novo Nordisk Foundation grant NNF10CC1016517. E.K. was supported by Deutsche Forschungsgemeinschaft (DFG, GRK1772, GRK 2290 and TRR175) and by People Programme (Marie Sk?odowska-Curie Actions H2020-MSCA-ITN-2015-675585). F.K. was supported by the Russian Foundation for Basic Research, 17-00-00296, Institute of Computational Technologies of SB RAS, Novosibirsk, 630090, Russian Federation (PI: Fedor Kolpakov). J.K. was supported by grants R35-GM119771 and P41-EB023912 from the NIH (US) to the Icahn School of Medicine. P.K. was supported by NIH grant GM075742 from the NIH (US) to SRI International. S.K. was supported by grant 031L104B (de.NBI partner project ?ModSim?) by the German Federal Ministry of Education and Research to MPI Magdeburg. L.M.L. was supported by grant P41-GM103313 from the NIH (US) to the University of Connecticut School of Medicine. P.M. was supported by grant GM080219 from the NIH (US). P.T.M was supported by grant PTDC/EEI-CTP/2914/2014 from Funda??o para a Ci?ncia e a Tecnologia (FCT) to INESC-ID. A.P.'s contribution to this manuscript is a follow-up of the work done while employed at Virginia Tech. (VA, US). The opinions expressed in this manuscript are the authors? own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States Government. S.C.S. was supported by grant U19-AI117873 from the NIH (US). Funding Information: G.B. was supported by National Resource for Network Biology (NRNB, US), award 5P41‐GM103504. Funding Information: S.C.S. was supported by grant U19‐AI117873 from the NIH (US). Funding Information: J.{\v C}. was supported by the Czech Research Infrastructure Infrastructure for Systems Biology C4SYS, project LM2015055; GA {\v C}R, grant 18‐24397S; and the MEYS of the Czech Republic under OP RDE grant CZ.02.1.01/0.0/0.0/16_026/0008413 “Strategic Partnership for Environmental Technologies and Energy Production”. Funding Information: J.K. was supported by grants R35‐GM119771 and P41‐EB023912 from the NIH (US) to the Icahn School of Medicine. Funding Information: P.K. was supported by NIH grant GM075742 from the NIH (US) to SRI International. Funding Information: P.T.M was supported by grant PTDC/EEI‐CTP/2914/2014 from Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (FCT) to INESC‐ID. Funding Information: P.M. was supported by grant GM080219 from the NIH (US). Funding Information: R.F. was supported by the U.S. Department of Energy, Offices of Advanced Scientific Computing Research and the Biological and Environmental Research as part of the Scientific Discovery Through Advanced Computing program, grant DE‐SC0010429. Funding Information: S.K. was supported by grant 031L104B (de.NBI partner project “ModSim”) by the German Federal Ministry of Education and Research to MPI Magdeburg. Funding Information: M.G.G. was supported by European Molecular Biology Laboratory (EMBL) core funding. Publisher Copyright: {\textcopyright} 2020 California Institute of Technology Published under the terms of the CC BY 4.0 license",

year = "2020",

month = aug,

day = "1",

doi = "10.15252/msb.20199110",

language = "English",

volume = "16",

journal = "Molecular Systems Biology",

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publisher = "Nature Publishing Group",

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}

TY - JOUR

T1 - SBML Level 3

T2 - an extensible format for the exchange and reuse of biological models

AU - Keating, Sarah M.

AU - Waltemath, Dagmar

AU - König, Matthias

AU - Zhang, Fengkai

AU - Dräger, Andreas

AU - Chaouiya, Claudine

AU - Bergmann, Frank T.

AU - Finney, Andrew

AU - Gillespie, Colin S.

AU - Helikar, Tomáš

AU - Hoops, Stefan

AU - Malik-Sheriff, Rahuman S.

AU - Moodie, Stuart L.

AU - Moraru, Ion I.

AU - Myers, Chris J.

AU - Naldi, Aurélien

AU - Olivier, Brett G.

AU - Sahle, Sven

AU - Schaff, James C.

AU - Smith, Lucian P.

AU - Swat, Maciej J.

AU - Thieffry, Denis

AU - Watanabe, Leandro

AU - Wilkinson, Darren J.

AU - Blinov, Michael L.

AU - Begley, Kimberly

AU - Faeder, James R.

AU - Gómez, Harold F.

AU - Hamm, Thomas M.

AU - Inagaki, Yuichiro

AU - Liebermeister, Wolfram

AU - Lister, Allyson L.

AU - Lucio, Daniel

AU - Mjolsness, Eric

AU - Proctor, Carole J.

AU - Raman, Karthik

AU - Rodriguez, Nicolas

AU - Shaffer, Clifford A.

AU - Shapiro, Bruce E.

AU - Stelling, Joerg

AU - Swainston, Neil

AU - Tanimura, Naoki

AU - Wagner, John

AU - Meier-Schellersheim, Martin

AU - Sauro, Herbert M.

AU - Palsson, Bernhard

AU - Bolouri, Hamid

AU - Kitano, Hiroaki

AU - Funahashi, Akira

AU - Hermjakob, Henning

AU - Doyle, John C.

AU - Hucka, Michael

AU - Adams, Richard R.

AU - Allen, Nicholas A.

AU - Angermann, Bastian R.

AU - Antoniotti, Marco

AU - Bader, Gary D.

AU - Červený, Jan

AU - Courtot, Mélanie

AU - Cox, Chris D.

AU - Dalle Pezze, Piero

AU - Demir, Emek

AU - Denney, William S.

AU - Dharuri, Harish

AU - Dorier, Julien

AU - Drasdo, Dirk

AU - Ebrahim, Ali

AU - Eichner, Johannes

AU - Elf, Johan

AU - Endler, Lukas

AU - Evelo, Chris T.

AU - Flamm, Christoph

AU - Fleming, Ronan M.T.

AU - Fröhlich, Martina

AU - Glont, Mihai

AU - Gonçalves, Emanuel

AU - Golebiewski, Martin

AU - Grabski, Hovakim

AU - Gutteridge, Alex

AU - Hachmeister, Damon

AU - Harris, Leonard A.

AU - Heavner, Benjamin D.

AU - Henkel, Ron

AU - Hlavacek, William S.

AU - Hu, Bin

AU - Hyduke, Daniel R.

AU - de Jong, Hidde

AU - Juty, Nick

AU - Karp, Peter D.

AU - Karr, Jonathan R.

AU - Kell, Douglas B.

AU - Keller, Roland

AU - Kiselev, Ilya

AU - Klamt, Steffen

AU - Klipp, Edda

AU - Knüpfer, Christian

AU - Kolpakov, Fedor

AU - Krause, Falko

AU - Kutmon, Martina

AU - Laibe, Camille

AU - Lawless, Conor

AU - Li, Lu

AU - Loew, Leslie M.

AU - Machne, Rainer

AU - Matsuoka, Yukiko

AU - Mendes, Pedro

AU - Mi, Huaiyu

AU - Mittag, Florian

AU - Monteiro, Pedro T.

AU - Natarajan, Kedar Nath

AU - Nielsen, Poul M.F.

AU - Nguyen, Tramy

AU - Palmisano, Alida

AU - Pettit, Jean Baptiste

AU - Pfau, Thomas

AU - Phair, Robert D.

AU - Radivoyevitch, Tomas

AU - Rohwer, Johann M.

AU - Ruebenacker, Oliver A.

AU - Saez-Rodriguez, Julio

AU - Scharm, Martin

AU - Schmidt, Henning

AU - Schreiber, Falk

AU - Schubert, Michael

AU - Schulte, Roman

AU - Sealfon, Stuart C.

AU - Smallbone, Kieran

AU - Soliman, Sylvain

AU - Stefan, Melanie I.

AU - Sullivan, Devin P.

AU - Takahashi, Koichi

AU - Teusink, Bas

AU - Tolnay, David

AU - Vazirabad, Ibrahim

AU - von Kamp, Axel

AU - Wittig, Ulrike

AU - Wrzodek, Clemens

AU - Wrzodek, Finja

AU - Xenarios, Ioannis

AU - Zhukova, Anna

AU - Zucker, Jeremy

N1 - Funding Information: A.G. was supported by the Japanese Society for the Promotion of Science. Funding Information: D.K. was supported by Novo Nordisk Foundation grant NNF10CC1016517. Funding Information: M.G. was supported by funding to HITS from the German Federal Ministry of Education and Research (BMBF) as part of the Liver Systems Medicine Network LiSyM (FKZ 031L0056) and through the MulticellML project (FKZ 01ZX1707B), as well as from the European Union Horizon2020 framework programme of the European Commission under Grant Agreement 825843 and from the Klaus Tschira Foundation (KTS). Funding Information: D.D. was supported by grant iLite (Innovations for LIver and Tissue Engineering) from Agence nationale de la recherche (ANR, France) to INRIA, Paris, France; by grant LiSyM (Liver Systems Medicine) from Bundesministerium für Bildung und Forschung (BMBF, Germany) to IfADo, Dortmund, Germany; by grant VLN (Virtual Liver Network) from Bundesministerium für Bildung und Forschung (BMBF, Germany) to IfADo, Dortmund, Germany; by grant Physicancer from Institut national de la santé et de la recherche médicale (INSERM, France) to INRIA, Paris, France; and by grant NOTOX (Predicting long‐term toxic effects using computer models based on systems characterisations of organotypic cultures) from EU 7 Framework Programme to INRIA, Paris, France. th Funding Information: L.M.L. was supported by grant P41‐GM103313 from the NIH (US) to the University of Connecticut School of Medicine. Funding Information: M.L.B. was supported by grant P41‐GM103313 and R01‐GM095485 from the NIH (US) to the University of Connecticut School of Medicine. Funding Information: E.K. was supported by Deutsche Forschungsgemeinschaft (DFG, GRK1772, GRK 2290 and TRR175) and by People Programme (Marie Skłodowska‐Curie Actions H2020‐MSCA‐ITN‐2015‐675585). Funding Information: B.A.'s work on SBML Level 3 was supported by the National Institutes of Health (NIH, US) and he is currently employed by AstraZeneca. Funding Information: F.K. was supported by the Russian Foundation for Basic Research, 17‐00‐00296, Institute of Computational Technologies of SB RAS, Novosibirsk, 630090, Russian Federation (PI: Fedor Kolpakov). Funding Information: W.S.H. was supported by grant R01‐GM111510 from the National Institute of General Medical Sciences (NIGMS, US) of the NIH. Funding Information: C.E. was supported by CHARME, COST, Action CA15110 MoU (PI: Chris Evelo) to Maastricht University. Funding Information: We sincerely thank all current and past SBML users, developers, contributors, supporters, advisors, administrators, and community members. We give special thanks to the following people for contributions and support: Jim Anderson, Nadia Anwar, Gordon Ball, Duncan B?renguier, Upinder Bhalla, Fr?d?ric Y. Bois, Benjamin Bornstein, Richard Boys, Ann Chasson, Thomas Cokelaer, Marco Donizelli, Alexander D?rr, Marine Dumousseau (Sivade), Lisa Falk, David Fange, Ed Frank, Ralph Gauges, Martin Ginkel, Nail Gizzatkulov, Victoria Gor, Igor Goryanin, Ryan N. Gutenkunst, Arnaud Henry, Stefanie Hoffmann, Duncan Hull, Dagmar Iber, Gael Jalowicki, Henrik Johansson, Akiya Jouraku, Devesh Khandelwal, Thomas B. L. Kirkwood, Victor Kofia, Benjamin L. Kovitz, Bryan Kowal, Andreas Kremling, Ursula Kummer, Hiroyuki Kuwahara, Anuradha Lakshminarayana, Nicolas Le Nov?re, Thomas S. Ligon, Adrian Lopez, Timo Lubitz, Peter Lyster, Natalia Maltsev, Jakob Matthes, Joanne Matthews, Tommaso Mazza, Eric Minch, Sebastian Nagel, Maki Nakayama, Poul M. F. Nielsen, German Nudelman, Anika Oellrich, Nobuyuki Ohta, Michel Page, Victoria Petri, Ranjit Randhawa, Veerasamy Ravichandran, Elisabeth Remy, Isabel Rojas, Ursula Rost, Jan D. Rudolph, Takayuki Saito, Takeshi Sakurada, Howard Salis, Maria J. Schilstra, Marvin Schulz, Shalin Shah, Daryl Shanley, Tom Shimizu, Jacky Snoep, Hugh D. Spence, Yves Sucaet, Linda Taddeo, Jose Juan Tapia, Alex Thomas, Jannis Uhlendorf, Martijn P. van Iersel, Marc Vass, Jonathan Webb, Katja Wengler, Benjamin Wicks, Sarala Wimalaratne, Haoran Yu, Thomas J. Zajac, W. Jim Zheng, and Jason Zwolak. The principal authors thank many funding agencies for their support of this work. F.B., A.D., M.H., T.M.H., S.M.K., B.O., and L.S., as well as SBML.org and its online resources, were supported by the National Institute of General Medical Sciences (NIGMS, US), grant R01-GM070923 (PI: Hucka). In addition, F.B. has been supported by the Bundesministerium f?r Bildung und Forschung (BMBF, DE), grant de.NBI ModSim1, 031L0104A (PI: Ursula Kummer). M.L.B. has been supported by NIH (US) grant P41-GM103313 and R01-GM095485. A.D. has been supported by infrastructural funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, and by the German Center for Infection Research (DZIF). A.F. was supported by the Grant-in-Aid for Young Scientists (B), grant 21700328 from JSPS KAKENHI (JP) to Keio University. J.F. was supported by National Institutes of Health (NIH, US) grant P41-GM103712 to the National Center for Multiscale Modeling of Biological Systems (MMBioS). H.H. was supported by the Biotechnology and Biological Sciences Research Council (BBSRC, UK) ?MultiMod? project (grant BB/N019482/1). T.H. was supported by NIH (US) grant 5R35-GM119770-03 to the University of Nebraska?Lincoln. S.H. was supported by NIGMS (US) grant R01-GM080219. M.K. was supported by the Federal Ministry of Education and Research (BMBF, DE), research network Systems Medicine of the Liver (LiSyM), grant 031L0054, Humboldt-University Berlin (PI: K?nig). A.L. was supported by the BBSRC (UK) while working at the Centre for Integrated Systems Biology of Ageing and Nutrition (CISBAN), Newcastle University. C.M. was supported by the National Science Foundation (NSF, USA) under grant CCF-1748200 and CCF-1856740. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF. I.M. was supported by NIH grant P41-EB023912 and P41-GM103313. K.R. was supported by the Department of Biotechnology, Government of India (grant BT/PR4949/BRB/10/1048/2012). M.M.-S. was supported by the Intramural Research Program of NIAID, NIH (US). R.M.-S. was supported by the BBSRC (UK) ?MultiMod? project (grant BB/N019482/1). B.P.'s was supported by NIH (US) grant GM57089 to the University of California, San Diego, and by the Novo Nordisk Foundation Grant NNF10CC1016517. H.M.S. was supported by NIGMS (US) grant R01-GM123032 (PI: Sauro) and by the National Institute of Biomedical Imaging and Bioengineering (NIBIB, US) grant P41-EB023912 (PI: Sauro). J.C.S. was supported by NIGMS (US) grant P41-GM103313. M.S. was supported by the DDMoRe program (EU), Innovative Medicines Initiative Joint Undertaking under grant agreement 115156. N.S. was supported by BBSRC (UK) grant ?Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM) ?, grant BB/M017702/1 (PI: Nigel S. Scrutton). F.Z. was supported by the Intramural Research Program of NIAID, NIH (US). We also thank the Google Summer of Code program for support of SBML software development. B.A.'s work on SBML Level 3 was supported by the National Institutes of Health (NIH, US) and he is currently employed by AstraZeneca. G.B. was supported by National Resource for Network Biology (NRNB, US), award 5P41-GM103504. M.L.B. was supported by grant P41-GM103313 and R01-GM095485 from the NIH (US) to the University of Connecticut School of Medicine. J.?. was supported by the Czech Research Infrastructure Infrastructure for Systems Biology C4SYS, project LM2015055; GA ?R, grant 18-24397S; and the MEYS of the Czech Republic under OP RDE grant CZ.02.1.01/0.0/0.0/16_026/0008413 ?Strategic Partnership for Environmental Technologies and Energy Production?. D.D. was supported by grant iLite (Innovations for LIver and Tissue Engineering) from Agence nationale de la recherche (ANR, France) to INRIA, Paris, France; by grant LiSyM (Liver Systems Medicine) from Bundesministerium f?r Bildung und Forschung (BMBF, Germany) to IfADo, Dortmund, Germany; by grant VLN (Virtual Liver Network) from Bundesministerium f?r Bildung und Forschung (BMBF, Germany) to IfADo, Dortmund, Germany; by grant Physicancer from Institut national de la sant? et de la recherche m?dicale (INSERM, France) to INRIA, Paris, France; and by grant NOTOX (Predicting long-term toxic effects using computer models based on systems characterisations of organotypic cultures) from EU 7th Framework Programme to INRIA, Paris, France. C.E. was supported by CHARME, COST, Action CA15110 MoU (PI: Chris Evelo) to Maastricht University. R.F. was supported by the U.S. Department of Energy, Offices of Advanced Scientific Computing Research and the Biological and Environmental Research as part of the Scientific Discovery Through Advanced Computing program, grant DE-SC0010429. A.G. was supported by the Japanese Society for the Promotion of Science. M.G. was supported by funding to HITS from the German Federal Ministry of Education and Research (BMBF) as part of the Liver Systems Medicine Network LiSyM (FKZ 031L0056) and through the MulticellML project (FKZ 01ZX1707B), as well as from the European Union Horizon2020 framework programme of the European Commission under Grant Agreement 825843 and from the Klaus Tschira Foundation (KTS). M.G.G. was supported by European Molecular Biology Laboratory (EMBL) core funding. W.S.H. was supported by grant R01-GM111510 from the National Institute of General Medical Sciences (NIGMS, US) of the NIH. D.K. was supported by Novo Nordisk Foundation grant NNF10CC1016517. E.K. was supported by Deutsche Forschungsgemeinschaft (DFG, GRK1772, GRK 2290 and TRR175) and by People Programme (Marie Sk?odowska-Curie Actions H2020-MSCA-ITN-2015-675585). F.K. was supported by the Russian Foundation for Basic Research, 17-00-00296, Institute of Computational Technologies of SB RAS, Novosibirsk, 630090, Russian Federation (PI: Fedor Kolpakov). J.K. was supported by grants R35-GM119771 and P41-EB023912 from the NIH (US) to the Icahn School of Medicine. P.K. was supported by NIH grant GM075742 from the NIH (US) to SRI International. S.K. was supported by grant 031L104B (de.NBI partner project ?ModSim?) by the German Federal Ministry of Education and Research to MPI Magdeburg. L.M.L. was supported by grant P41-GM103313 from the NIH (US) to the University of Connecticut School of Medicine. P.M. was supported by grant GM080219 from the NIH (US). P.T.M was supported by grant PTDC/EEI-CTP/2914/2014 from Funda??o para a Ci?ncia e a Tecnologia (FCT) to INESC-ID. A.P.'s contribution to this manuscript is a follow-up of the work done while employed at Virginia Tech. (VA, US). The opinions expressed in this manuscript are the authors? own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States Government. S.C.S. was supported by grant U19-AI117873 from the NIH (US). Funding Information: G.B. was supported by National Resource for Network Biology (NRNB, US), award 5P41‐GM103504. Funding Information: S.C.S. was supported by grant U19‐AI117873 from the NIH (US). Funding Information: J.Č. was supported by the Czech Research Infrastructure Infrastructure for Systems Biology C4SYS, project LM2015055; GA ČR, grant 18‐24397S; and the MEYS of the Czech Republic under OP RDE grant CZ.02.1.01/0.0/0.0/16_026/0008413 “Strategic Partnership for Environmental Technologies and Energy Production”. Funding Information: J.K. was supported by grants R35‐GM119771 and P41‐EB023912 from the NIH (US) to the Icahn School of Medicine. Funding Information: P.K. was supported by NIH grant GM075742 from the NIH (US) to SRI International. Funding Information: P.T.M was supported by grant PTDC/EEI‐CTP/2914/2014 from Fundação para a Ciência e a Tecnologia (FCT) to INESC‐ID. Funding Information: P.M. was supported by grant GM080219 from the NIH (US). Funding Information: R.F. was supported by the U.S. Department of Energy, Offices of Advanced Scientific Computing Research and the Biological and Environmental Research as part of the Scientific Discovery Through Advanced Computing program, grant DE‐SC0010429. Funding Information: S.K. was supported by grant 031L104B (de.NBI partner project “ModSim”) by the German Federal Ministry of Education and Research to MPI Magdeburg. Funding Information: M.G.G. was supported by European Molecular Biology Laboratory (EMBL) core funding. Publisher Copyright: © 2020 California Institute of Technology Published under the terms of the CC BY 4.0 license

PY - 2020/8/1

Y1 - 2020/8/1

N2 - Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.

AB - Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.

KW - computational modeling

KW - file format

KW - interoperability

KW - reproducibility

KW - systems biology

UR - http://www.scopus.com/inward/record.url?scp=85089933733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85089933733&partnerID=8YFLogxK

U2 - 10.15252/msb.20199110

DO - 10.15252/msb.20199110

M3 - Review article

C2 - 32845085

AN - SCOPUS:85089933733

VL - 16

JO - Molecular Systems Biology

JF - Molecular Systems Biology

SN - 1744-4292

IS - 8

M1 - e9110

ER -

SBML Level 3: an extensible format for the exchange and reuse of biological models

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