Multiscale Systems Biology Working Group

Multiscale Systems Biology Working Group

Working Group leads: Aleksander PopelDan BeardMike 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

2013 Meeting

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:

Monday, September 17, 2012

Multi-Scale Modeling of Sickle Cell Anemia

George Karniadakis, PhD, Brown University

Archived Recording:

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:

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)
CellSys, a modular software tool for simulation of growth and organization processes in multicellular systems in 2D and 3D implementing agent-based modeling
Chaste (Cancer, Heart and Soft Tissue Environment), a general purpose multi-scale simulation package
Dymola (Dynamic Modeling Laboratory, a complete tool for modeling and simulation of integrated and complex systems based on the open Modelica modeling language)
DYNSTOC: a tool for simulating large-scale rule-based models
E-cell Project
FLAME, Flexible Large-scale Agent Modelling Environment
Gepasi (Biochemical Kinetics Simulator)
JDesigner (Visual Network Design Tool)
JSim: Open source simulation system for full VVUQ modeling and reproducibility, from data to parameter evaluation.
MASON (Multi-Agent Simulator Of Neighborhoods… or Networks; discrete-event multiagent simulation library core in Java)
MCell and DReAMM (Center for Quantitative Biological Simulation Microphysiology Gateway)
Modelica (an object-oriented, equation based language to model complex physical systems)
NetLogo (Multi-Agent Modeling)
NFsim (the network-free stochastic simulator, an open-source, modeling and simulation platform for biology)
RULEMONKEY: a tool for simulating large-scale rule-based models
SemSim (multi-scale model modularity, semantic annotation)
Systems Biology Workbench
TinkerCell (Visual Network Design Tool)
Virtual Cell

Sensitivity and Uncertainty Analysis Tools
eFAST (Extended Fourier Amplitude Sensitivity Test)
LHS (Latin Hypercube Sampling)
LHS-PRCC (Latin Hypercube Sampling - Partial Rank Correlation Coefficient)
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.

NCBI (National Center for Biotechnology Information - genomic, proteomic, PubMed)
Biositemaps, a mechanism for computational biologists and bioinformaticians to openly broadcast and retrieve meta-data about biomedical resources
The DrugBank database
HMDB (The Human Metabolome Database)
MiMI (Michigan Molecular Interactions)
PathCase: Pathways Database System
PhysioNet (biomedical signals database)
ProteinLounge (signaling pathways; Pathway Builder software)
SMPDB (The Small Molecule Pathway Database)
The UCSD-Nature Signaling Gateway
The Visible Human Project

Model Databases/Repositories
BioModels Database
Cardiovascular Model Repository
CellML Models
Neuromuscular Models Library
Physiome Model Repository of (mainly ) transport models: 
Ricordo (Virtual Physiological Human project) 

Imaging/Visualization Tools
Cytoscape (An Open Source Platform for Complex-Network Analysis and Visualization)
MCV (Multiscale Spatiotemporal Visualisation, Development of an Open-Source Software Library for the Interactive Visualisation of Multiscale Biomedical Data)
NA-MIC (National Alliance for Medical Image Computing)
NIfTI (Neuroimaging Informatics Technology Initiative)
3D Slicer (An open source software platform for visualization and medical image computing)
V3D (3D/4D/5D Image Visualization & Analysis System for Bioimages & Surface Objects)

Markup Languages
SBGN (Systems Biology Graphical Notation)

The Gene Ontology (GO)
The Open Biological and Biomedical Ontologies
The Sequence Ontology
Systems Biology Ontology (SBO)

Relevant Project Portals
The Physiome Project
The Virtual Physiological Human
BioNetWiki/BioNetGen, a resource for rule-based modeling 
The Virtual Physiological Rat 
COMBINE, the COmputational Modeling in BIology NEtwork

Standards Under Development
SED-ML (Simulation Experiment Description Markup Language)
SBOL (Synthetic Biology Open Language)

Disease- and Organ-Specific Resources
Human Body Simulator (Integrated Human Physiology):
NCI thesaurus
The Cardiac Atlas Project
SimVascular Cardiovascular Modeling and Simulation Application
The Virtual Gastrointestinal Tract
The Quantitative Kidney Database
The Virtual Liver

Educational Resources
Physiome Model Repository: Open source models and tutorials. Then click "Tutorials".
The Virtual Physiological Rat Project YouTube Channel

Human Body Simulator (Integrated Human Physiology):

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:


Multiscale Systems Biology: A Special Issue Devoted to Understanding Biology and Medicine Across Multiple Scales, Annals of Biomedical Engineering, November 2012
IEEE Transactions on Biomedical Engineering, Special Issue on Multiscale Modeling and Analysis in Computational Biology and Medicine Volume: 58 , Issue: 10 , Part: 2 
Multiscale Modeling of Particle Interactions: Applications in Biology and Nanotechnology. M.R. King and D.J. Gee, editors, Wiley, 2010 
Engineering in Medicine and Biology Magazine, IEEE Vol 28 , Issues:2- 3, 2009 

List of Participants:

Systems Biology Working Group Participants

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