Toward community standards and software for whole-cell modeling

Objective: Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in the Systems Biology Markup Language. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance: We anticipate that these new standards and software will enable more comprehensive models.

Chris J. Myers | Daewon Lee | Anna Zhukova | Dagmar Waltemath | Michael Hucka | Ilya Kiselev | Falk Schreiber | Arne T. Bittig | Rafael S. Costa | Leandro H. Watanabe | Florian Wendland | Arthur P. Goldberg | Jonathan R. Karr | Kieran Smallbone | Wolfram Liebermeister | Vasundra Touré | Christian Knüpfer | Matteo Cantarelli | Harold F. Gómez | J. Kyle Medley | Yin Hoon Chew | Natalie J. Stanford | Sucheendra K. Palaniappan | Frank T. Bergmann | Martin Scharm | Begum Alaybeyoglu | Je-Hoon Song | Vincent Knight-Schrijver | Markus Wolfien | Tobias Czauderna | Yan Zhu | Joseph Cursons | Pinar Pir | Pedro Mendes | Jannis Uhlendorf | James T. Yurkovich | Jens Hahn | Marcus Krantz | Hojjat Naderi-Meshkin | Vijayalakshmi Chelliah | Mahesh Sharma | Denis Kazakiewicz | Tom Theile | Nikita Mandrik | Bertrand Moreau | Argyris Zardilis | Matthias König | Audald Lloret-Villas | Tuure Hameri | Naveen K. Aranganathan | Kambiz Baghalian | Paulo E. Pinto Burke | Rafael S. Costa | Daniel F. Hernandez Gardiol | Daniel Priego-Espinosa | Milenko Tokic | Namrata Tomar | Thawfeek M. Varusai | A. P. Goldberg | Namrata Tomar | Pınar Pir | P. Mendes | Joseph Cursons | M. Hucka | J. Medley | M. König | Wolfram Liebermeister | K. Smallbone | F. Schreiber | C. Myers | Jens Hahn | Marcus Krantz | V. Chelliah | J. Yurkovich | Jannis Uhlendorf | N. Stanford | K. Baghalian | R. Costa | Milenko Tokic | Tuure Hameri | D. Gardiol | Argyris Zardilis | Je-Hoon Song | N. Mandrik | M. Wolfien | Begum Alaybeyoglu | I. Kiselev | H. Naderi-Meshkin | A. Zhukova | B. Moreau | D. Priego-Espinosa | Mahesh Sharma | Christian Knüpfer | Naveen K. Aranganathan | P. Burke | Matteo Cantarelli | D. Kazakiewicz | V. Knight-Schrijver | Daewon Lee | A. Lloret-Villas | F. Wendland | Yan Zhu | V. Touré | Tobias Czauderna | Dagmar Waltemath | S. K. Palaniappan | Martin Scharm | Tom Theile | Vasundra Touré | Vincent Knight-Schrijver | Vijayalakshmi Chelliah | Audald Lloret-Villas | Nikita Mandrik

[1]  Ruby Lee,et al.  WholeCellViz: data visualization for whole-cell models , 2013, BMC Bioinformatics.

[2]  Bonny Jain,et al.  Towards a whole-cell modeling approach for synthetic biology. , 2013, Chaos.

[3]  Chris J. Myers,et al.  Design and Test of Genetic Circuits Using ${\tt iBioSim}$iBioSim , 2012, IEEE Design & Test of Computers.

[4]  Herbert M. Sauro,et al.  Antimony: a modular model definition language , 2009, Bioinform..

[5]  Andreas Zell,et al.  Path2Models: large-scale generation of computational models from biochemical pathway maps , 2013, BMC Systems Biology.

[6]  Axel Kowald,et al.  Systems biology standards—the community speaks , 2007, Nature Biotechnology.

[7]  Jens Timmer,et al.  Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models , 2015, PLoS Comput. Biol..

[8]  Chris J. Myers,et al.  SBML Level 3 package: Hierarchical Model Composition, Version 1 Release 3 , 2015, J. Integr. Bioinform..

[9]  Lucila Ohno-Machado,et al.  Natural language processing: an introduction , 2011, J. Am. Medical Informatics Assoc..

[10]  Sarala M. Wimalaratne,et al.  The Systems Biology Graphical Notation , 2009, Nature Biotechnology.

[11]  Marta Z. Kwiatkowska,et al.  PRISM 4.0: Verification of Probabilistic Real-Time Systems , 2011, CAV.

[12]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

[13]  Benjamin M. Good,et al.  Crowdsourcing for bioinformatics , 2013, Bioinform..

[14]  Sb Ras,et al.  BioUML: VISUAL MODELING, AUTOMATED CODE GENERATION AND SIMULATION OF BIOLOGICAL SYSTEMS , 2006 .

[15]  Jeong Wook Lee,et al.  Systems metabolic engineering of microorganisms for natural and non-natural chemicals. , 2012, Nature chemical biology.

[16]  Derek N. Macklin,et al.  The future of whole-cell modeling. , 2014, Current opinion in biotechnology.

[17]  Dariusz Plewczynski,et al.  A combined systems and structural modeling approach repositions antibiotics for Mycoplasma genitalium , 2015, Comput. Biol. Chem..

[18]  James A. Glazier,et al.  libRoadRunner 2.0: a high performance SBML simulation and analysis library , 2022, Bioinformatics.

[19]  N. Kikuchi,et al.  CellDesigner 3.5: A Versatile Modeling Tool for Biochemical Networks , 2008, Proceedings of the IEEE.

[20]  Jonathan R. Karr,et al.  WholeCellKB: model organism databases for comprehensive whole-cell models , 2012, Nucleic Acids Res..

[21]  Gary D. Bader,et al.  Promoting Coordinated Development of Community-Based Information Standards for Modeling in Biology: The COMBINE Initiative , 2015, Front. Bioeng. Biotechnol..

[22]  Javier Carrera,et al.  Why Build Whole-Cell Models? , 2015, Trends in cell biology.

[23]  Christoph Steinbeck,et al.  ChEBI in 2016: Improved services and an expanding collection of metabolites , 2015, Nucleic Acids Res..

[24]  D. Gillespie.  Exact Stochastic Simulation of Coupled Chemical Reactions , 1977 .

[25]  A. Barabasi,et al.  Targets Drug Genomes Identify Novel Antimicrobial Staphylococcus Aureus of Multiple Reconstruction and Flux Balance Analysis Comparative Genome-scale Metabolic Supplemental Material , 2009 .

[26]  Chris J. Myers,et al.  Meeting report from the fourth meeting of the Computational Modeling in Biology Network (COMBINE) , 2011, Standards in Genomic Sciences.

[27]  Jonathan R. Karr,et al.  WholeCellSimDB: a hybrid relational/HDF database for whole-cell model predictions , 2014, Database J. Biol. Databases Curation.

[28]  Matthias Klapperstück,et al.  VANTED v2: a framework for systems biology applications , 2012, BMC Systems Biology.

[29]  Falk Schreiber,et al.  Editing, validating and translating of SBGN maps , 2010, Bioinform..

[30]  Yangyang Zhao,et al.  BioModels: ten-year anniversary , 2014, Nucleic Acids Res..

[31]  Jacky L. Snoep,et al.  Reproducible computational biology experiments with SED-ML - The Simulation Experiment Description Markup Language , 2011, BMC Systems Biology.

[32]  Jonathan R. Karr,et al.  The principles of whole-cell modeling. , 2015, Current opinion in microbiology.

[33]  B. Palsson,et al.  Systems approach to refining genome annotation , 2006, Proceedings of the National Academy of Sciences.

[34]  Arthur P. Goldberg,et al.  Toward Scalable Whole-Cell Modeling of Human Cells , 2016, SIGSIM-PADS.

[35]  W. J. Hedley,et al.  A short introduction to CellML , 2001, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[36]  Julio R. Banga,et al.  A cooperative strategy for parameter estimation in large scale systems biology models , 2012, BMC Systems Biology.

[37]  Jonathan R. Karr,et al.  Accelerated discovery via a whole-cell model , 2013, Nature Methods.

[38]  Mudita Singhal,et al.  COPASI - a COmplex PAthway SImulator , 2006, Bioinform..

[39]  Joshua A. Lerman,et al.  COBRApy: COnstraints-Based Reconstruction and Analysis for Python , 2013, BMC Systems Biology.

[40]  Michael Hucka,et al.  The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core , 2010, J. Integr. Bioinform..

[41]  Jonathan R. Karr,et al.  A Whole-Cell Computational Model Predicts Phenotype from Genotype , 2012, Cell.

[42]  Stephen R. Heller,et al.  InChI - the worldwide chemical structure identifier standard , 2013, Journal of Cheminformatics.