This talk was part of the 2020 Disease Map Modeling Community meeting, covering the steps towards publishing reproducible simulation studies (based on a reused model). Links to different COMBINE guidelines, tutorials and efforts. Grants: European Commission: EOSCsecretariat.eu - EOSCsecretariat.eu (831644)

1. Prof. Dr. Dagmar Waltemath
Medical Informatics Laboratory
University Medicine Greifswald
dagmarwaltemath
Adding value to scientific results
COMBINE standards & guidelines
for systems medicine modeling
Disease Maps Community Meeting | November 13, 2020 | slideshare

2. Medical Informatics Lab @ University
Medicine Greifswald (Germany)
• Extraction, storage, harmonisation
of clinical research data
• FAIRification of research data in
medicine and population-based
studies
SEMS @ University of Rostock
• Reproducibility | Reusability of
model-based results
• de.NBI data management for
German Bioinformatics network
2
Who is MILA?

3. 3
Who is MILA?
2020
2019
2010
Medical Informatics Lab @ University
Medicine Greifswald (Germany)
• Extraction, storage, harmonisation
of clinical research data
• FAIRification of research data in
medicine and population-based
studies
SEMS @ University of Rostock
• Reproducibility | Reusability of
model-based results
• de.NBI data management for the
German Bioinformatics network

4. Hospital
information
system
How can we share COVID-19
data globally – and make
sense out of it?
What does MILA do?
4

5. • Technical aspects
• Database aspects
• Human aspects
• Data modeling
How can we share research
data in a sustainable and
effective way as to avoid
dublication, loss of knowledge,
and mis-interpretation?
What does MILA do?
5
How can we share COVID-19
data globally – and make
sense out of it?

6. paper-based reporting
reproducible studies
6
We benefit from experiences with
standards development in systems
biology.

7. 7
Extensive curation leads to higher
quality leads to increased trust.
Easy access access leads to
increased visibility.
Easy executability leads to
increased collaboration.
Better reproducibility
leads to increased reuse.
Reproducible studies mean
better scientific practise.

8. Data formatsGuidelines
COMBINE coordinates the standards
developments in systems biology.
Semantic layer
Editorial Boards
Specifications
Software tool support
Mailing lists
Annual meetings
8
https://co.mbine.org/

9. How can I make use of the
COMBINE infrastructure to build
and provide better models?
9
What is missing for
Disease Maps people?
www.menti.com
(code 79 85 93 5)

10. 1. Reuse a published study.
Download model
Run model
Reuse model
correct
not correct
Modify model
10
Model
fits?
Results
correct
?
fit
no fit

11. Physiome Model Repository
• Models arranged in
workspaces (git)
• Summary and curation
status, Licence, visual
• Different views on
model
• Version comparison
• COMBINE Archive
https://models.physiomeproject.org
1. Reuse a published study.
11

12. BioModels
• Provides models and
associated files
• Keeps file history
• Description of model
components
• Curation results,
metadata, tagging,
• Detailed curation
https://www.ebi.ac.uk/biomodels/
1. Reuse a published study.
12

13. Screenshot (2020-11-10): https://www.ebi.ac.uk/biomodels/BIOMD0000000144#Overview
1. Reuse a published study.
13

14. 1. Reuse a published study.
14
Fig.: Keating Waltemath et al (2020) SBML Level 3: an extensible format for the exchange and reuse of
biological models. Molecular Systems Biology, 16(8), p.e9110
What does SBML
cover?
http://co.mbine.org/standards

15. 1. Reuse a published study.
15
Fig.: Schreiber et al (2020) Specifications of standards in systems and synthetic biology: status and
developments in 2020. Journal of integrative bioinformatics, 17(2-3). https://doi.org/10.1515/jib-2018-0013
How do I find the
latest spec?

16. 1. Reuse a published study.
16
Screenshot: Frank Bergmann, Bruce E. Shapiro and Michael Hucka. SBML Software Matrix.
http://sbml.org/SBML_Software_Guide/SBML_Software_Matrix (accessed 2020-11-12)
Which tool can
analyse my model?
https://amici.readthedocs.io/
296 tools
listed

17. 2. Manage your data to avoid
errors and information loss.
• Where did you get the original model from?
• Under what licence can you reuse it?
• Which versions of the model exist, which one are you going
to use?
• When and where did you retrieve it?
• Maybe there are better models that you can use – what was
the process of deciding for a specific one?
• How do you store all this information and how do you
encode the meta-data?
17

18. 18
12/11/14 © 2009 UNIVERSITÄT ROSTOCK | Fakultät für Informatik und Elektrotechnik
https://fairdomhub.org/
2. Manage your data to avoid
errors and information loss.

19. 3. Verify your hypotheses.
Design your model
Analyse model
Modify model
Modify simulation
Generate archive
Syntax
correct
?
Result
correct
?
19
syntax wrong
syntax OK
output differs
output OK

20. 4. (Re)Draw a meaningful network.
20
Mol Syst Biol, Volume: 3, Issue: 1, First published:
31 July 2007, DOI: (10.1038/msb4100171)
Touré et al (2018) Quick tips for creating effective and impactful biological pathways using the Systems
Biology Graphical Notation. PLoS Comput Biol 14(2): e1005740. https://doi.org/10.1371/journal.pcbi.1005740

21. 4. (Re)Draw a meaningful network
Screenshot (2020-11-10): https://sbgn.github.io/ https://sbgn.github.io/software_support
21

22. 5. Semantically enrich your model.
1. Use technical standards to encode semantic annotations, e.g. RDF, identifiers.org URIs and
BioModels.net qualifiers
2. Store annotations in a separate file: normalize the format in which annotations are stored
3. Develop a software library for support of semantic annotation standards
4. Develop standards-compliant software, promote consistency in annotation practices
5. Document which knowledge resources should be used for annotation and why: publicly
available documentation, e.g. Curation guidelines for a collaborative development of the
COVID-19 Disease Map
6. Establish a repository of reusable annotations: reduce the time required for annotation and
promote inter-annotator consistency
7. Ensure high-quality semantic annotations through training and quality control processes:
specific, complete and consistent annotations, e.g. https://www.ebi.ac.uk/biomodels-
static/jummp-biomodels-help/annotating_models.html
8. Establish and maintain collaborations with knowledge resource developers
22
Neal et al (2019) Harmonizing semantic annotations for computational models in biology, Briefings in
Bioinformatics 20:2, https://doi.org/10.1093/bib/bby087

23. 6. Archive your results.
https://combinearchive.org/software/
23
Bergmann et al (2014) COMBINE archive and OMEX format: one file to share all information to
reproduce a modeling project. BMC bioinformatics 15:1, https://doi.org/10.1186/s12859-014-0369-z

24. 24
6. Archive your results.
Scharm & Waltemath (2016) A fully featured COMBINE archive of a simulation study on syncytial mitotic
cycles in Drosophila embryos. F1000Research 5:2421. https://doi.org/10.12688/f1000research.9379.1

25. 6. Archive your results.
25
Scharm & Waltemath (2016) A fully featured COMBINE archive of a simulation study on syncytial mitotic
cycles in Drosophila embryos. F1000Research 5:2421. https://doi.org/10.12688/f1000research.9379.1

26. 7. Provide your study.
https://www.ebi.ac.uk/biomodels/
http://bigg.ucsd.edu/ http://www.opensourcebrain.org/
https://jjj.bio.vu.nl/
26

27. 27
7. Provide your study.
Scharm & Waltemath (2015) Extracting reproducible simulation studies from model repositories using the CombineArchive
Toolkit. BTW http://www.btw-2015.de/res/proceedings/Workshops/DMS/Scharm-Extracting_reproducible_sim.pdf
https://cat.bio.informatik.uni-rostock.de/

28. 7. Provide your study.
Submit your
COVID-19 model
here, get the CA
for free.
https://www.ebi.ac.uk/biomodels/covid-19 (through EOSC OVID-19 fast track funding)
28

29. 8. Check out the guidelines and
tutorials for further help.
10 tips for building useful SBGN maps Building fully featured COMBINE archives
29

30. 30
Reproduce a simulation Detect differences
http://sed-ml.org/
http://sysbioapps.spdns.org/SED-ML_Web_Tools
https://github.com/SemsProject/BiVeS https://most.bio.informatik.uni-rostock.de/
https://yomost.bio.informatik.uni-rostock.de/
Frank
Bergmann
David
Nickerson
Martin
Scharm
Tom
Gebhardt
Vasundra
Touré
Understand model evolution
Merge model versions
9. Check for tools to support you
(biased selection).

31. 31
Bundle all files in one archive Retrieve models efficiently Link models and other data
https://github.com/MaSyMoShttps://combinearchive.org/ https://covidgraph.org/
Wolfgang
Müller
Ron
Henkel
Mariam
Nassar
Martin
Peters
Henkel et al (2015) Combining computational models, semantic annotations and simulation experiments in
a graph database. Oxford DATABASE
2 experiments,
3 model versions,
changes, meta-data
9. Check for tools to support you
(biased selection).
Martin
Preusse
Lea
Gütebier

32. Conclusion
If your work is available,
documented and open…
32
…then others can host it, share
it, cite it, and advertise it!
Drawings: Anna Zhukova
What is missing for
Disease Maps people?
www.menti.com
(code 79 85 93 5)

33. 10th COMBINE Forum (2019)
https://doi.org/10.1515/jib-2020-0005
BioPAX
(G.D. Bader)
SBOL Visual
(T Gorochowski)
SBML
(Sarah Keating)
SBOL & Chair
(Chris Myers)
CellML
(David Nickerson)
SED-ML
(Matthias König)
NeuroML
(Padraig Gleeson)
Martin
Golebiewski
Semantics, med inf & vice-chair
(Dagmar Waltemath)
11th COMBINE Forum (2020) twitter
10. Join the crowd.
33
SBGN
(Falk Schreiber)

34. Dagmar Waltemath
Medical Informatics Lab &
Core Unit Research Data Management
University Medicine Greifswald
0000-0002-5886-5563
Image source: Wikimedia Commons, Creative Commons
Attribution-Share Alike 4.0 International
Join MILA 