Multiscale Systems Biology Working Group
Working Group leads: Aleksander Popel, Dan Beard, Mike King
Goals and Objectives:
This working group is devoted to multiple-scale analysis and simulation of biological systems, with a special emphasis on cellular phenomena. Our first goal is to establish on this site a clearinghouse of up-to-date information on available tools, novel concepts, and major relevant review papers in the field. This resource will aim to capture the state of the art in significant research, for purposes of advancing research, education, and training. Secondary goals include identifying and articulating current challenges and opportunities in the field, as well as fostering scientific collaborations.
Participation in Working Group:
Participation in this working group (WG) is open to all who are interested; to join please contact one of the WG co-leads listed above. WG participants will be kept appraised of WG, Multiscale Modeling (MSM) Consortium, and IMAG discussions. Responsibilities of this working group include: (i) defining the WG title, goals and objectives, (ii) determining the current state of the art in multiscale systems biology, and identifying new challenges and opportunities, and (iii) suggesting and attending webinar presentations, contributing to WG white papers, workshops and publications. Participants will be expected to actively engage in WG activities, including managing content on the site, participating in online presentations, and other relevant activities (MSM participants are assigned IMAG wiki logins by IMAG staff). The activities of the WG should not reflect someone’s personal agenda, but should represent the consensus of the group.
MSM Meetings
Upcoming Presentations
Tuesday March 11, 2014
Biocellion: Accelerating Computer Simulation of Multicellular Biological System Models
Seunghwa Kang, Nick Flann, Simon Kahan, Ilya Shmulevich
Past Presentations
Detailed List of Past Presentations (with abstracts)
Thursday March 21, 2013
Towards predictive quantitative modeling of tissue organization and tumor growth on histological scales by imaging, image analysis and modeling
Dirk Drasdo, Stefan Hoehme, Jan G. Hengstler, Rolf Gebhardt, Ursula Klingmueller, Jens Timmer
Wednesday, November 14, 2012
Modeling cardiac function and dysfunction
Natalia Trayanova, PhD, Johns Hopkins University
Archived Recording: https://webmeeting.nih.gov/p75536528/
Monday, September 17, 2012
Multi-Scale Modeling of Sickle Cell Anemia
George Karniadakis, PhD, Brown University
Archived Recording: https://webmeeting.nih.gov/p78189808/
Friday June 8, 2012
Specification, Construction, and Exact Reduction of State Transition System Models of Biochemical Processes
Scott M. Bugenhagen and Daniel A. Beard, PhD, Medical College of Wisconsin
Archived Recording: https://webmeeting.nih.gov/p65832122/
Friday October 28, 2011
Computational Bridging of Epithelial Morphogenesis and Tumor Mutations
Kasia A. Rejniak, PhD, H. Lee Moffitt Cancer Center & Research Institute
Imaging vascular dynamics
Lance L. Munn, PhD, Massachusetts General Hospital & Harvard Medical School
Tuesday May 31, 2011 The Cardiovascular System and Disease
Translating multi-scale modelling to the Heart of the clinic: developing personalised cardiac models
Nicolas Smith, Kings College London
Multiscale model of platelet adhesion and thrombus formation: validation with the humanized mouse
Michael King, Cornell University
Relevant Infrastructure:
Simulation Tools
BISEN (Biochemical Simulation Environment) http://www.virtualrat.org/BISEN/
CellSys, a modular software tool for simulation of growth and organization processes in multicellular systems in 2D and 3D implementing agent-based modelinghttp://msysbio.com/software/cellsys/
Chaste (Cancer, Heart and Soft Tissue Environment), a general purpose multi-scale simulation package http://web.comlab.ox.ac.uk/chaste/
CompuCell3D http://www.compucell3d.org/
Copasi http://www.copasi.org/
Dymola (Dynamic Modeling Laboratory, a complete tool for modeling and simulation of integrated and complex systems based on the open Modelica modeling language)http://www.dymola.com/
DYNSTOC: a tool for simulating large-scale rule-based models http://public.tgen.org/dynstoc/
E-cell Project http://www.e-cell.org/ecell/
FLAME, Flexible Large-scale Agent Modelling Environment http://www.flame.ac.uk/
Gepasi (Biochemical Kinetics Simulator) http://www.gepasi.org/
JDesigner (Visual Network Design Tool) http://www.sys-bio.org
JSim: Open source simulation system for full VVUQ modeling and reproducibility, from data to parameter evaluation. http://nsr.bioeng.washington.edu/jsim/
MASON (Multi-Agent Simulator Of Neighborhoods… or Networks; discrete-event multiagent simulation library core in Java) http://cs.gmu.edu/~eclab/projects/mason/
MCell and DReAMM (Center for Quantitative Biological Simulation Microphysiology Gateway) http://www.mcell.psc.edu/
Modelica (an object-oriented, equation based language to model complex physical systems) https://modelica.org/
NetLogo (Multi-Agent Modeling) http://ccl.northwestern.edu/netlogo/
NFsim (the network-free stochastic simulator, an open-source, modeling and simulation platform for biology) http://emonet.biology.yale.edu/nfsim/
OpenCell http://www.cellml.org/tools/opencell
OpenCMISS http://www.cmiss.org/openCMISS
RULEMONKEY: a tool for simulating large-scale rule-based models http://public.tgen.org/rulemonkey/
SemSim (multi-scale model modularity, semantic annotation) http://sbp.bhi.washington.edu/projects/semsim
Systems Biology Workbench http://www.sys-bio.org
TinkerCell (Visual Network Design Tool) http://www.tinkercell.com
Virtual Cell http://www.nrcam.uchc.edu/
Sensitivity and Uncertainty Analysis Tools
eFAST (Extended Fourier Amplitude Sensitivity Test) http://malthus.micro.med.umich.edu/lab/usadata/
LHS (Latin Hypercube Sampling) http://www.mathworks.com/matlabcentral/fileexchange/4352-latin-hypercube-sampling
LHS-PRCC (Latin Hypercube Sampling - Partial Rank Correlation Coefficient) http://malthus.micro.med.umich.edu/lab/usadata/
ME-PCM (Multi-element probabilistic collocation method) Foo J, Sindi S, Karniadakis GE. Multi-element probabilistic collocation for sensitivity analysis in cellular signalling networks. IET Syst Biol. 2009 3:239-254.
PLSDA (Partial Least Squares Discriminant Analysis) Westerhuis JA, van Velzen EJ, Hoefsloot HC, Smilde AK. Multivariate paired data analysis: multilevel PLSDA versus OPLSDA. Metabolomics. 2010 6:119-128.
SIMLAB http://simlab.jrc.ec.europa.eu/
Databases
NCBI (National Center for Biotechnology Information - genomic, proteomic, PubMed) http://www.ncbi.nlm.nih.gov/
Biositemaps, a mechanism for computational biologists and bioinformaticians to openly broadcast and retrieve meta-data about biomedical resources http://biositemaps.ncbcs.org/
The DrugBank database http://www.drugbank.ca/
HMDB (The Human Metabolome Database) http://www.hmdb.ca/
MiMI (Michigan Molecular Interactions) http://mimi.ncibi.org/MimiWeb/main-page.jsp
PathCase: Pathways Database System http://nashua.case.edu/PathwaysWeb/
PhysioNet (biomedical signals database) http://www.physionet.org/
ProteinLounge (signaling pathways; Pathway Builder software) http://www.proteinlounge.com/
SMPDB (The Small Molecule Pathway Database) http://www.smpdb.ca/
The UCSD-Nature Signaling Gateway http://www.signaling-gateway.org/
The Visible Human Project http://www.nlm.nih.gov/research/visible/
Model Databases/Repositories
BioModels Database http://biomodels.net/, http://biomodels.org/
Cardiovascular Model Repository https://simtk.org/home/cv-gmodels/
CellML Models http://models.cellml.org/cellml
Neuromuscular Models Library https://simtk.org/home/nmblmodels/
Physiome Model Repository of (mainly ) transport models: http://www.physiome.org/Models
Ricordo (Virtual Physiological Human project) http://www.vph-noe.eu/vph-projects/74-eu-fp7-vph-projects/390-ricordo
Imaging/Visualization Tools
Cytoscape (An Open Source Platform for Complex-Network Analysis and Visualization) http://www.cytoscape.org/
MCV (Multiscale Spatiotemporal Visualisation, Development of an Open-Source Software Library for the Interactive Visualisation of Multiscale Biomedical Data) http://www.msv-project.eu/
NA-MIC (National Alliance for Medical Image Computing) http://www.na-mic.org/
NIfTI (Neuroimaging Informatics Technology Initiative) http://nifti.nimh.nih.gov/
3D Slicer (An open source software platform for visualization and medical image computing) http://www.slicer.org/
V3D (3D/4D/5D Image Visualization & Analysis System for Bioimages & Surface Objects) http://penglab.janelia.org/proj/v3d/V3D/
Markup Languages
SBML http://sbml.org
CellML http://www.cellml.org/
FieldML http://www.physiome.org.nz/xml_languages/fieldml
SBGN (Systems Biology Graphical Notation) http://sbgn.org/Main_Page
Ontologies
The Gene Ontology (GO) http://www.geneontology.org/
The Open Biological and Biomedical Ontologies http://www.obofoundry.org/
The Sequence Ontology http://www.sequenceontology.org/
Systems Biology Ontology (SBO) http://www.ebi.ac.uk/sbo/main/
Relevant Project Portals
The Physiome Project http://www.physiome.org.nz/, http://www.physiome.org/
The Virtual Physiological Human http://www.vph-noe.eu/
BioNetWiki/BioNetGen, a resource for rule-based modeling http://bionetgen.org/index.php/Main_Page
The Virtual Physiological Rat http://www.virtualrat.org
COMBINE, the COmputational Modeling in BIology NEtwork http://co.mbine.org
Standards Under Development
SED-ML (Simulation Experiment Description Markup Language) http://www.biomodels.net/sed-ml/
SBOL (Synthetic Biology Open Language) http://www.sbolstandard.org/M
Disease- and Organ-Specific Resources
Human Body Simulator (Integrated Human Physiology):
HumMod http://hummod.org/
Cancer:
caBIG https://cabig.nci.nih.gov/
NCI thesaurus http://ncit.nci.nih.gov/
Cardiovascular:
The Cardiac Atlas Project http://www.cardiacatlas.org/
SimVascular Cardiovascular Modeling and Simulation Application https://simtk.org/home/simvascular/
Gastrointestinal:
The Virtual Gastrointestinal Tract http://www.vigorpp.eu/
Kidney:
The Quantitative Kidney Database http://physiome.ibisc.fr/qkdb/
Liver:
The Virtual Liver http://www.virtual-liver.de/
Educational Resources
Physiome Model Repository: Open source models and tutorials. http://www.physiome.org/Models/ Then click "Tutorials".
The Virtual Physiological Rat Project YouTube Channel http://www.youtube.com/user/VirtualRatProject
Human Body Simulator (Integrated Human Physiology):
HumMod http://hummod.org/
Challenges and Opportunities:
High-throughput genomic, proteomic and epigenomic data are rapidly accumulating. Current models of physiological systems rarely take advantage of the availability of such data, in part because they inform process that operate on different time and space scales. Thus, a challenge and opportunity for multiscale systems biology is utilize statistical modeling and analyses dealing with high-throughput data to inform mechanistic multiscale modeling.
Another challenge for the physics-based models is for computationally intensive simulations to reach to laboratory and experimental timescales to enable direct comparison between models and experimental data. There is a trade-off between efficient course-graining, and retaining connection to meaningful physical parameters that correspond to independently measurable quantities. Some of these issues will hopefully be addressed in the context of blood clot formation, in a special multiscale Biorheology session of the International Society on Thrombosis and Haemostasis this summer:
http://www.ssc2012.org/porgramme/index.php/friday-ssc-sessions/biorheology
References:
Multiscale Systems Biology: A Special Issue Devoted to Understanding Biology and Medicine Across Multiple Scales, Annals of Biomedical Engineering, November 2012http://link.springer.com/article/10.1007%2Fs10439-012-0661-x
IEEE Transactions on Biomedical Engineering, Special Issue on Multiscale Modeling and Analysis in Computational Biology and Medicine Volume: 58 , Issue: 10 , Part: 2http://ieeexplore.ieee.org/xpl/tocresult.jsp?isnumber=6082051&punumber=10
Multiscale Modeling of Particle Interactions: Applications in Biology and Nanotechnology. M.R. King and D.J. Gee, editors, Wiley, 2010http://onlinelibrary.wiley.com/book/10.1002/9780470579831
Engineering in Medicine and Biology Magazine, IEEE Vol 28 , Issues:2- 3, 2009 http://ieeexplore.ieee.org/search/searchresult.jsp?punumber=51&searchWithin=multiscale