Whole Cell Volkswagen Summer School - a SEMS Project

http://sems.uni-rostock.de
Markus Wolfien
markus.wolfien@uni-rostock.de
Standardising Karr’s Whole Cell Model
24.02.2014
Research Seminar

http://sems.uni-rostock.de
Karr‘s Whole Cell Model of Mycoplasma genitalium
2
• First in silico Whole Cell Model
• Why M.genitalium ? Bacterium with the smallest known genome – 525 genes
European consortium determined the transcriptome (Guell et al., 2009),
proteome (Kuhner et al.,2009), and metabolome (Yus et al., 2009)
• Benefits ?
(1) Describes the life cycle of a single cell at molecular level
(2) Accounts the specific function of every annotated gene product
(3) Predicts a wide range of observable cellular behaviors
• Effort ? Based on 900 publications, 116 m.files and more than 1,900
experimentally observed parameters
sci-collections.tumblr.com

http://sems.uni-rostock.de 3
• Workflow and Model overview

Figure 1: Whole cell model architecture (Karr et al. 2012a)

16 state variables
that drive the
model (m)
28 submodules
processes that occur in
the cell (n)
Figure 2: Whole cell model architecture and summary of state variables and submodules(Karr et al. 2012a)

• Challenge:
• Whole model is encoded in Matlab-file format, and is therefore not accessible
to the broad modeler community
• To run, edit and work with the model you have to be comfortable with Matlab
language and the complex structure of the model – thousands of source code
lines more or less sufficiently described
• Limited reusability

• Challenge:
• Solution:

• Challenge:
• Solution:
Standardisation of the Whole Cell Model

SEMS is getting involved
• Aim:
Encoding the Whole Cell Model into the current xml standards formats
• Free and open standard with widespread software support and a
community of users and developers
• Can represent many different classes of biological phenomena

SEMS is getting involved
• Aim:
Encoding the Whole Cell Model into the current xml standards formats
• Free and open standard with widespread software support and a
community of users and developers
• Can represent many different classes of biological phenomena
SBML – Systems Biology Markup Language (Hucka et al. 2003)
SED-ML – Simulation Experiment Description Markup
Language (Waltemath et al. 2011)
GO – Gene Ontology and other bio-ontologies
(Ashburner et al. 2000)

Volkswagen Summer School
“Combining standards for today’s models”

Volkswagen Summer School
“Combining standards for today’s models”
• Funding application sent in January 2014
• Anticipated date for summer school in late September 2014 for one week in
Rostock
• Around 60 participants
• STANDARD DEVELOPERS: Experts from the standard-developing
COMBINE community and tool developers
• COORDINATORS: Scientific research staff who is familiar with the
COMBINE standards and infrastructure
• RESEARCH TEAMS: Modelers from different bioinformatics and
systems biology areas, young researchers

Volkswagen Summer School – Goals
(1) Providing a reusable, standards-compliant version of the Whole Cell Model
to the community
(2) Teaching young researchers how to take advantage of scientific results
encoded in standard formats
(3) Demonstrating the power of standard formats
(4) Establishing a roadmap for standard development in systems biology based
on the gaps and needs identified during the summer school

Volkswagen Summer School – Involved Researchers
Dagmar Waltemath
University of Rostock
Jonathan Karr
Stanford University
Falk Schreiber
IPK Gatersleben
Frank Bergmann
University of Heidelberg
Nicolas Le Novère
Babraham Institute
BioModels Database Team
EMBL-EBI
Wolfram Liebermeister
Humboldt University

Volkswagen Summer School – Involved Researchers
Dagmar Waltemath
University of Rostock
Jonathan Karr
Stanford University
Falk Schreiber
IPK Gatersleben
Frank Bergmann
University of Heidelberg
Nicolas Le Novère
Babraham Institute
BioModels Database Team
EMBL-EBI
Wolfram Liebermeister
Humboldt University
… and you?

Volkswagen Summer School – Scientific Gain
• For the community:
• Open access to a reusable version of the modules that form the Whole
Cell Model
• Visibility of the COMBINE community, promotion of the use of
standards, better understanding of needs and aims of the different partners
(modellers, developers)
• Training of young modelers who will carry this knowledge into the
different labs and thereby increase the acceptance of standard formats
• For the standard developers:
• Evaluation of current standards
• Promotion of standard development to modelers, in particular young
researchers

Volkswagen Summer School – Further Information
• SEMS – Volkswagen Summer School Project
https://sems.uni-rostock.de/workshops/volkwagen-summer-school-
project/
• Google group for information about the current status of the Summer school
https://groups.google.com/forum/#!forum/wholecell-symposium
• Google Project to share source codes of the Whole Cell Model pre Summer
School – GIT repository
http://code.google.com/p/wholecell/

Volkswagen Summer School – Further Information
Figure 3: Example of whole cell visualisation by http://wholecellviz.stanford.edu/

References
Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight,
S.S., Eppig, J.T., et al. (2000). Gene ontology: tool for the unification of biology. The Gene Ontology
Consortium. Nat Genet 25, 25-29.
Guell, M., van Noort, V., Yus, E., Chen, W.H., Leigh-Bell, J., Michalodimitrakis, K., Yamada, T., Arumugam, M.,
Doerks, T., Kuhner, S., et al. (2009). Transcriptome complexity in a genome-reduced bacterium. Science 326,
1268-1271.
Hucka, M., Finney, A., Sauro, H.M., Bolouri, H., Doyle, J.C., Kitano, H., Arkin, A.P., Bornstein, B.J., Bray, D.,
Cornish-Bowden, A., et al. (2003). The systems biology markup language (SBML): a medium for
representation and exchange of biochemical network models. Bioinformatics 19, 524-531.
Karr, J.R., Sanghvi, J.C., Macklin, D.N., Gutschow, M.V., Jacobs, J.M., Bolival, B., Jr., Assad-Garcia, N., Glass,
J.I., and Covert, M.W. (2012). A whole-cell computational model predicts phenotype from genotype. Cell
150, 389-401.
Kuhner, S., van Noort, V., Betts, M.J., Leo-Macias, A., Batisse, C., Rode, M., Yamada, T., Maier, T., Bader, S.,
Beltran-Alvarez, P., et al. (2009). Proteome organization in a genome-reduced bacterium. Science 326, 1235-
1240.
Waltemath, D., Adams, R., Bergmann, F.T., Hucka, M., Kolpakov, F., Miller, A.K., Moraru, II, Nickerson, D.,
Sahle, S., Snoep, J.L., et al. (2011). Reproducible computational biology experiments with SED-ML--the
Simulation Experiment Description Markup Language. BMC Syst Biol 5, 198.
Yus, E., Maier, T., Michalodimitrakis, K., van Noort, V., Yamada, T., Chen, W.H., Wodke, J.A., Guell, M., Martinez,
S., Bourgeois, R., et al. (2009). Impact of genome reduction on bacterial metabolism and its regulation.
Science 326, 1263-1268.

Whole Cell Volkswagen Summer School - a SEMS Project

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