The Physiome Project

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The Physiome Project

• Rob MacLeod
• CVRTI/BE/SCII
• Peter Hunter
• Auckland University

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What is the Physiome?
The Physiome Project is an integrated program
whose mission is to archive and disseminate
quantitative data and models of the functional
behavior of biological molecules, cells, tissues,
organs, and organisms.

• Bassingthwaighte (1995) Advances in Experimental
  Medicine and Biology 1995382331-9)
• coined the term for the first time

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Proposed Projects

• 1.Brain and CNS
• 2.Heart and cardiovascular system
• 3.Lungs and respiratory system
• 4.Kidney and urinary system
• 5.Musculo-skeletal system
• 6.Alimentary system
• 7.Reproductive system
• 8.Endocrine system
• 9.Haemolymphoid system
• 10.Integumental system

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Physiome Bioinformatics
Modeling Hierarchies
Databases

• Genes
• Proteins
• Biophysical models
• Constitutive laws
• Organ model
• Whole body model

• Genome
• Protein
• Physiology
• Structural
• Bioeng. Materials
• Clinical

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Mathematical Models

• Level 1 models Molecular models
• Level 2 models Subcellular Markov models
• Level 3 models Subcellular ODE models
• Level 4 models Tissue and whole organ continuum
  models
• Level 5 models Whole body continuum models
• Level 6 models Whole body system models

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Visualization Tools

• Interrogation of model parameters
• Animated visualization of computational output
• From molecular level through to the whole body
• Web based
• Coupled to the computational models in a
  user-friendly fashion.

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Instrumentation

• Structural measurements
• geometry and tissue microstructure of organs
• present methods too slow and tedious
• Material property measurements
• mechanical, electrical, thermal, etc
• variety of species
• pathological conditions
• nonlinear, coupled parameters

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Physiome Groups

• BioNoME (UCSD)
• Biology Network of Modeling Efforts limited
  activity but good pedigree
• funded by Procter and Gamble for 3 years
• Cardiome Project (Auckland)
• the model and most active group
• Microcirculatory Physiome Project (Johns Hopkins)
• seems well supported and active
• Endotheliome Project
• Pulmonary Physiome

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Physiome Links

• www.ornl.gov/TechResources/Human_Genome/faq/faqs1.
  html
• the mother of all bioscience megaprojects
• bionome.sdsc.edu/
• source of some data and info
• www.physiome.org/
• the home site poorly maintained
• www.esc.auckland.ac.nz/People/Staff/Hunter/physiom
  e.html
• the best place to start the search
• http//www.esc.auckland.ac.nz/sites/physiome/index
  .html
• home of the MLs
• www.bme.jhu.edu/news/microphys/
• microcirculatory physiome project
• http//www.physiome.com/
• the company
• www.IBB.gatech.edu/HiltonHead/hiltonheadworkshop.h
  tml
• the next relevant meeting on the physiome

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BioNoME Project (UCSD)

• Biology Network of Modeling Efforts
• Funded by Procter and Gamble for 3 years
• Contains interface to models that run on remote
  supercomputer (at UCSD)
• Only biophysical models are Beeler-Reuter and
  Luo-Rudy I
• Anatomical models of the heart and
  microcirculation
• Limited activity but good pedigree

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Microcirculation Physiome
Thus, we propose to develop a database of the
microcirculation that encompasses anatomical and
functional data with mathematical and
computational models, computational engines, and
tools for integration.

• Many particpants (based at JHU)
• U Western Ontario, Auckland, U Tennessee, U
  Virginia, JHU, U Arizona
• Projects
• anatomy, e.g., using GIS
• functional descriptions of microcirculation,
  transport, etc.

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Cardiome Project
Tissue Structure
Anatomy
Heart model
Tissue properties
Cellular properties
Drug Discovery Clinical Applications
Model Validation
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Cardiome Groups
AU David Bullivant Peter Hunter Ian LeGrice Denis
Loiselle Poul Nielsen Andrew Pullan Bruce
Smaill Alistair Young JHU Bill Hunter Eduardo
Marban Sasha Popel Rai Winslow UCSF Julius
Guccione Mark Ratcliffe
UCSD Jim Covell Andrew McCulloch Jeff
Omens MIT Colin Brennan Forbes Dewey Ian
Hunter Maastricht Theo Arts Frits Prinzen Rob
Reneman Utah Chris Johnson Rob MacLeod Bruno
Taccardi
Physiome Sciences Tom Colatsky Gang Chen Adam
Muzikant Oxford Chris Bradley Martyn Nash Peter
Kohl Denis Noble Nic Smith UW (Seattle) Jim
Bassingthwaighte Eric Feigl Zheng Li Technion
Israel Sam Sideman et al
Duke Craig Henriquez et al Tulane Natalia
Trayanova et al. Lausanne Nathalia Virag et
al CWRU Yoram Rudy et al Columbia Kevin
Costa Jeff Holmes
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Anatomy

• Completed or underway
• Vent. geom. fibre-sheet structure for dog (AU)
• Vent. geom. fibre-sheets for rabbit (UCSD, JHU)
• Coronary anatomy for pig (UCSD)
• Atrial geometry structure for pig (UCSD, AU,
  ...)
• Cardiac valve structure (AU)
• Automated measurement rig (AU MIT)
• Needed soon
• Geom. fibre-sheet structure for pig, human
• Geom. fibre-sheet structure for hypertrophy etc

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Mechanics

• Completed or underway
• Material properties -
• biaxial tests on dog myocardium (AU)
• shear testing of pig myocardium (AU)
• torsion testing of rabbit pap. muscle (JHU)
• ECM structure (UCSD, Columbia, AU, JHU)
• Functional studies on gene targetted mice (UCSD)
• Infarct modelling (UCSD, Columbia, AU)
• Ventricular aneurysm (UCSF)
• Acute ischaemia (UCSD, UWash)
• Needed soon
• Microstructure mechanical properties of
  cytoskeleton ECM

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Activation

• Completed or underway
• Ionic current models (CWRU, Oxford, JHU, Calgary,
  PS, ....)
• Spatial distribution of ion channels (PS)
• SA, atrial, AV, HIS, Purkinje (Oxford, AU)
• Reentrant arrhythmias (many)
• Defibrillation studies (many)
• Heart failure (JHU)
• Mutations (eg KvLQT1/minK -gt IKs -gt LQTS)
• EC coupling
• CellML (AU, PS)
• Needed soon
• Spatial distribution of gap junctions
• Drugs -gt models -gt clinically observable effects
• Mutations (eg HERG -gt IKr -gt LQTS)
• Expression profiling in acquired heart disease

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Energy Supply Metabolism

• Completed or underway
• Coronary flow (AU)
• Coronary flow regulation (UW)
• Metabolism energetics (UW, Oxford, AU)
• Ischaemia (Oxford, AU)
• Flux balance kinetic models (UCSD, CWRU)
• Needed soon
• Integration of different parts of metabolic
  pathway models
• with energy supply demand
• Coupling to electrophysiology generation of
  reentrant arrhythmias

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Databases
Cell
Tissue
Organ(ism)

• Structure and spatial parameters
• Material properties
• Dynamic behavior
• Documentation
• Communications and interactions

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CellML
Cell
CellML
Code
MathML
Graphics
C Fortran Java Tcl/Tk/Perl
http//www.esc.auckland.ac.nz/sites/physiome/cellm
l/pages/index.html
http//www.physiome.com/
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XML
www.w3.org/XML/

• XML is a method for putting structured data in a
  text file
• XML looks a bit like HTML but isn't HTML
• XML is text, but isn't meant to be read
• XML is a family of technologies
• XML is verbose, but that is not a problem
• XML is new, but not that new
• XML is license-free, platform-independent and
  well-supported
• (Note supports MathML!)

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CellML Basics

• Experiment (simulation)
• model description
• preparation (species, boundary conditions, other
  conditions)
• variables (to overwrite those extracted from and
  existing database)
• independent variables (time, space)
• experimental results (from simulation)
• Model description most advanced component

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FieldML/AnatML
Geometry
Organ(ism)
Conductvities
AnatML FieldML
Code
MathML
Graphics
C Fortran Java Tcl/Tk/Perl
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AnatML

• ltbody partgt
• description of geometry
• uses CMISS data structures
• ltbody groupgt
• links to other body parts
• ltplacementgt
• location of the body part in space

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MeshML/FieldML/RegionML

• MeshML
• elements of the geometry with connectivities
• FieldML
• basis functions
• field parameters
• RegionML
• container for meshes and fields

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The Future of the Physiome

• Support from other labs
• Cooperation between labs
• Funding
• Technical challenges
• Our role?????