sems project overview

Model and simulation management for systems biology

Dagmar Waltemath, Ron Henkel, Martin Scharm, Olaf Wolkenhauer

Dept. of Systems Biology and Bioinformatics

University of Rostock

[email protected]

06.12.2012 Model and simulation management | D. Waltemath

mailto:[email protected]



Models, models, models

2 06.12.2012 Model and simulation management | D. Waltemath

And that‘s why we need systems biology! http://www.cs.uofs.edu/~varrialer2/

Models, models, models


And that‘s why we need model management! http://www.cs.uofs.edu/~varrialer2/

Challenge: Model reuse

On the left: Goldbeter, 1991 (Proc Natl Acad Sci) view of the cdc2 kinase. On the right:

Gardner's extension of that model with a Cyclin inhibitor, Gardner et al., 1998 (Proc Natl Acad

Sci) (Fig. taken from original publications, extended by M. Scharm)


Challenge: Result reproducibility

“[..] in Biomodel database the model BIOMD0000000139 and BIOMD0000000140

are two different models and they are supposed to show different results. Unfortunately

simulating them in Copasi gives same result for both the models. [..] “

(on sbml-discuss)


Challenge: Result reproducibility

“[..] in Biomodel database the model BIOMD0000000139 and BIOMD0000000140

are two different models and they are supposed to show different results. Unfortunately

simulating them in Copasi gives same result for both the models. [..] “

(on sbml-discuss)

(Figures produced by Frank Bergmann in SBW Workbench)

Reply: Where is the problem?


Field of research

Management

Model Version

Control

Simulation

Version Control

Model

Storage

Simulation

Storage

Model

Search

Simulation

Search


Model Version Control Model Search Model Storage

Model version control enables the study of a model’s history and ensures long-term availability of results. (More: M. Scharm)

Model management: Version control

- Model history How did this model change in the past? Which parts? When?

- Difference detection What changed in this version?

- Change presentation Which parts of the model changed most frequently?


Model management: Storage

- Annotated model code SBML, CellML, NeuroML, …, MIRIAM URNs,

identifiers.org

- Model structure

- Linked models and simulation experiments Which models on yeast

show sustained oscillations?

Graph-based storage incorporates structural information and experiments in the search. (More: R. Henkel)



Ranked model retrieval supports users in quickly finding relevant models. (More: R. Henkel)

Model management: Search

- Find models by annotation Which models exist about Gluconeogenesis?

- Find model by structure Which models investigate the production of

lacZ/β-Galactosidase?

- Rank models Which model is the most suitable to study glycolytic

oscillations? And why?



SED-ML improves result reproducibility and enables the linking of experiments to models. (More: D. Waltemath)

Simulation Management

- Standard formats for simulation encoding SED-ML, MIASE, KiSAO

- Linking models and simulation Which experiments are available for my

yeast metabolism model?

- Consistency checks Can I perform my analysis on this version of Ulf’s

model?


Simulation VC Simulation Search Simulation Storage

SEMS: Methods for Model & Simulation Management

• XML version control

• Difference detection in XML Waltemath et al., submitted

• Ranked model retrieval Henkel et al., 2010 (BMC Bioinf)

• Structure- and

ontology-based search

Simulation VC SimulationSearch Simulation Storage

• Relational databases Waltemath et al., 2011 (DBSpektrum)

• Graph-based storage Henkel et al., 2012 (INFORMATIK)

• Standardized encoding of simulation setups Waltemath et al., 2011 (BMC SysBiol)

• Linking models and simulation descriptions Henkel et al., 2012 (INFORMATIK)

Model Search Model Version control Model Storage


References

06.12.2012 Model and simulation management | D. Waltemath 13

Goldbeter , 1991 (Proc Natl Acad Sci ) Goldbeter A. A minimal cascade model for the mitotic oscillator

involving cyclin and cdc2 kinase.

Gardner et al., 1998 (Proc Natl Acad Sci ) Gardner TS, Dolnik M, Collins JJ. A theory for controlling cell

cycle dynamics using a reversibly binding inhibitor.

Waltemath et al. (submitted ) Waltemath D et al. (under revision) On improving model reuse and result

reproducibility through version control for computational models of biological systems.

Waltemath et al., 2011 (BMC SysBiol) Waltemath D, Adams R, Bergmann FT, Hucka M, Kolpakov F, et

al. (2011)Reproducible computational biology experiments with SED-ML - The Simulation Experiment

Description Markup Language BMC Systems Biology 2011, 5:198

Henkel et al., 2010 (BMC Bioinf) Henkel R, Endler L, Peters A, Le Novère N & Waltemath D (2010):

Ranked retrieval of Computational Biology models. BMC Bioinformatics, 11(423)

Henkel et al., 2012 (INFORMATIK) R. Henkel, N. le Novère, O. Wolkenhauer, D. Waltemath (2012)

Consideratons of graph-based concepts to manage computational biology models and associated

simulations. In: 4. Workshop über Daten in den Lebenswissenschaften: Datenbanken als

Kommunikationszentrum, INFORMATIK 2012, Brunswig, Germany.

Waltemath et al., 2011 (DBSpektrum) Waltemath D, Henkel R, Meyer H & Heuer A (2011): Das Sombi-

Framework zum Ermitteln geeigneter Suchfunktionen für biologische Modelldatenbasen. Datenbank-

Spektrum.

sems project overview

Education