COMBINE & de.NBI Tutorial: Modelling and Simulation Tools in Systems Biology



Dates: Thursday October 31st, 2019 (9:00 - 18:00)
Location: Okinawa Insitute of Science and Technology Graduate University, Okinawa, Japan

Hosted by: HITS - Heidelberg Institute for Theoretical Studies


This tutorial workshop is a satellite of the 20th International Conference on Systems Biology (ICSB).
Participants will learn how to set up computer models of biological systems (e.g. metabolic or signalling networks) using experimental kinetic data and how to simulate them in different systems biology platforms. Hands-on sessions, lectures and software demonstrations will be included, providing attendees with the necessary skills to access experimental kinetics data from available resources, to assemble computer models with these data, and finally to simulate the generated models using simulation tools. Also handling and exchange of biological models based on existing community standards will be demonstrated along with the basic principles of the underlying standard formats and how they support reproducible and FAIR computational modelling.

The topics covered will include:
• Reproducibility and FAIR (Findable, Accessible, Interoperable and Re-usable) data
• Curation services
• Model setup using different software tools and systems biology platforms
• Using experimental data for setting up quantitative models
• Parameter estimation, optimization and model fitting
• Simulation, analysis and visualization of biochemical models, and multicellular modelling
• Constraint-based and logical modeling of metabolic and signaling networks
• Database supported modelling: integrated data management and model databases
• Community standards and formats for systems and synthetic biology models
• Machine learning for model reduction and image analysis

Target audience
Experimentalists and modellers with some very basic experience in modelling and simulation of biological networks and everybody who would like to learn more about the tools and standards. Attendees are expected to bring their own computer.


Tutors

Agenda

Registration

Location

Travel Information

Additional Information

Organization

Tutors


Agenda (tentative)

There will be short presentations about the covered tools, databases and modeling standards, as well as hands-on sessions and software demonstrations for practical training. It will be demonstrated how the different tools can be used in concerted modeling workflows.

Agenda outline:

09.00-10.30 Introduction lessons: Tools and Data Resources for Modeling and Simulation
09:00 – 09:15 Introduction (Martin Golebiewski, HITS, Heidelberg, Germany)
09:15 – 09:35 COMBINE (Martin Golebiewski, HITS, Heidelberg, Germany)
09:35 – 09:55 SABIO-RK (Andreas Weidemann, HITS, Heidelberg, Germany)
09:55 – 10:15 CellDesigner (Akira Funahashi, Keio University, Yokohama, Japan)
10:15 – 10:35 COPASI (Jürgen Pahle, Heidelberg University, Germany)

10.35-11.00 Coffee break

11.00-12.30 Introduction lessons: Tools and Data Resources for Modeling and Simulation
11:00 – 11:20 BioModels (Rahuman Sheriff, EMBL-EBI, Hinxton, UK)
11:20 – 11:40 Physiome Model Repository and OpenCOR (David Nickerson, University of Auckland, New Zealand)
11:40 – 12:00 Morpheus (Lutz Brusch and Jörn Starruß, TU Dresden, Germany)
12:00 – 12:20 Virtual Cell (VCell) (Ion Moraru, UConn Health, Farmington, CT, USA)
12:20 – 12:40 Tellurium (Veronica Porubsky, University of Washington, Seattle, WA, USA))
12:40 – 13:00 SEEK/FAIRDOMhub (Martin Golebiewski, HITS, Heidelberg, Germany)

13.00-14.00 Lunch break

14:00 – 18:00 Hands-on and demo sessions (all tutors)

There will be hands-on and demo sessions for these tools, platforms and databases given below.

Covered tools, platforms and databases

Introduced standard formats

Some commonly used community standards for model and modelling data exchange, as well as for model visualization will be introduced (SBGN, SBML, CellML, and SED-ML) in practical examples using the covered tools. More information about the standards can be found on the COMBINE (Computational Modeling in Biology Network) website: http://co.mbine.org

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Registration

The participation in the tutorial is free of charge but we are limited to 60 participants. Please register by October 13th, 2019 to help us best plan an optimal tutorial.

TUTORIAL REGISTRATION: https://forms.gle/5jDTUwViani5v82o9

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Travel Information

Please refer to the ICSB website for travel details:


Travel

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Preparation

Attendees are expected to bring their own computer for hands-on training.

In order to profit best from the offered training you should pre-install the following software:

CellDesigner

CellDesigner is a structured diagram editor for drawing gene-regulatory and biochemical networks. By using CellDesigner, you can browse and modify existing SBML models with references to existing databases, and simulate and view the dynamics through an intuitive graphical interface. Networks are able to link with simulation and other analysis packages through Systems Biology Workbench (SBW). CellDesigner supports simulation and parameter scan by an integration with SBML ODE Solver, SBML Simulation Core and Copasi.
Download and Install CellDesigner 4.4

COPASI

COPASI is a software tool for handling, simulating, and analysing kinetic models of biochemical reaction networks. It is intended for biologists who are not experts in numerical algorithms or programming languages. The tutorial will give an overview over the features of COPASI, such as deterministic and stochastic simulation, parameter scans, sensitivities and control analysis. It will then focus on parameter estimation. We will provide model files for download in this space, so if you want to follow along the presentation on your own computer, please download the latest COPASI version (currently Build 213) from the website http://www.copasi.org/ and install it on your computer.

CellNetAnalyzer

CellNetAnalyzer (CNA) is a MATLAB toolbox providing a graphical user interface and various (partially unique) computational methods and algorithms for exploring structural and functional properties of metabolic, signaling, and regulatory networks. Computations can be started within the GUI (interactive network maps) or from command line (via API functions).

Please prepare the tutorial beforehand:
1) Install MATLAB on your computer: http://www.mathworks.com/
2) Download CellNetAnalyzer via http://www2.mpi-magdeburg.mpg.de/projects/cna/cna.html/

and follow then the (few) instructions for installing.

Morpheus

Morpheus is a modeling and simulation environment for the study of multiscale and multicellular systems from interacting cell populations via embryonic pattern formation and morphogenesis to organ function. Morpheus provides a Graphical User Interface for easy model editing and workflow control as well as a repository of example models to start from without the need to code nor compile. It imports SBML models and allows to freely couple ODE, PDE and CPM models in 2D and 3D and to simulate them using adaptive solvers. Morpheus is open-source at gitlab (BSD license). Please download the ready-to-run installers for Windows, Linux or Mac OSX from http://morpheus.gitlab.io/#download

OpenCOR

OpenCOR (https://opencor.ws/) is an open source cross-platform modelling environment that can be used to organise, edit, simulate and analyse models described in the CellML format. It relies on a plugin-based approach, making it possible to support other standards (e.g. SED-ML), as well as add new capabilities.It can be run both as a command line interface (CLI) and graphical user interface (GUI) application. The CLI version is primarily used to run simulations in batch mode and convert CellML files to different formats (e.g., C, Fortran, Python), while the GUI version supports all of OpenCOR’s features.

Organisational plugins allow interaction with the Physiome Model Repository (PMR; https://models.physiomeproject.org) to access and update a user’s work held on PMR. Editing plugins are used to create and edit CellML and SED-ML files, and any text-based file. CellML files can be edited using a human-friendly format and annotated using RDF triples consisting of a CellML element, a BioModels.net qualifier and an ontological term.

A simulation plugin provides an environment for performing numerical simulations. Users can choose from a range of solvers, edit parameter values and initial conditions, as well as specify plots to draw. Simulations can be paused to alter their parameters before being resumed. They can also be imported and exported to SED-ML, making it possible to share simulation experiments in a reproducible manner.


You should also have a look at these online tools, databases and data management systems that will be introduced in detail during the tutorial workshop:

BioModels database

http://www.ebi.ac.uk/biomodels-main/

BioModels Database serves as a reliable repository of computational models of biological processes. It hosts models described in peer-reviewed scientific literature and models generated automatically from pathway resources (Path2Models). A large number of models collected from literature are manually curated and semantically enriched with cross-references from external data resources. The resource allows scientific community to store, search and retrieve mathematical models of their interest. In addition, features such as generation of sub-models, online simulation, conversion of models into different representational formats, and programmatic access via web services, are provided.

FAIRDOM SEEK

http://seek4science.org/

SEEK is a web-based platform, with associated tools, for finding, sharing and exchanging data, models and processes in Systems Biology. It is designed as data management platform to support systems biology consortia and distributed research networks. It is used, among others, in the European ERASysAPP (ERA-Net for Systems Biology Applications) network (http://www.erasysapp.eu/), as well as in the German Liver Systems Network LiSyM (http://www.lisym.org).

JWS Online

http://jjj.bio.vu.nl

JWS Online is both a repository of curated biochemical pathway models and a simulation tool for these models. Users are able to view the models in the database, select a particular model, alter its parameters and perform a simulation on it. JWS Online is based on a client-server architecture, with the calculations performed on the server side. All that is required on the client side is a browser which is able to run Java applets.

Physiome Model Repository

https://models.physiomeproject.org/

The Physiome Model Repository (PMR) is both an archive of curated mathematical models (primarily encoded in the CellML format) and associated simulation experiments, and a repository where you can actively work in a collaborative manner. Tools like OpenCOR are able to work directly with the PMR, enabling users to easily leverage powerful versioning and collaborative tools with minimum effort.

SABIO-RK

http://sabio.h-its.org/

SABIO-RK is a curated database that contains information about biochemical reactions, their kinetic rate equations with parameters and experimental conditions. The data is either manually extracted from published literature or directly submitted by experimenters. The system offers standardized data by the use of controlled vocabularies and annotations pointing to other resources and biological ontologies. SABIO-RK enables the access to kinetic data for experimentalists and modellers, supporting the setup of quantitative computer models.

Additional Information

Internet Access

The meeting rooms have wireless internet access. More information will be provided on-site.


Organization

Martin Golebiewski David Nickerson
Phone: +49-6221-533-281
Phone: +64-9-923-1994
HITS gGmbH
Auckland Bioengineering Institute
Schloss-Wolfsbrunnenweg 35
70 Symonds Street
D-69118 Heidelberg
Auckland 1010
Germany
New Zealand
http://www.h-its.org
http://www.abi.auckland.ac.nz/




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