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CellML Workshop 2012. Overview of recent developments in the VPH/ Physiome project. Maurice Wilkins Centre. 15 years of development. 1997 IUPS Physiome Committee. 1998 CellML , FieldML. 1999 Systems Biology Markup Language. 2003 IMAG (NIH, NSF, FDA, NASA, DOE, DOD, ..).
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CellML Workshop 2012 Overview of recent developments in the VPH/Physiome project Maurice Wilkins Centre
15 years of development .. 1997 IUPS Physiome Committee 1998 CellML, FieldML 1999 Systems Biology Markup Language 2003 IMAG (NIH, NSF,FDA, NASA, DOE, DOD, ..) 2006 STEP: Strategy for European Physiome2008 VPH Network of Excellence 2010 Drug Disease Model Resources (DDMoRe) 2011 VPH Institute
Standards for models, data & software Experimental measurements Minimum information standards: MIAME, MICEE, .. Data standards: DICOM, BioSignalML, .. Metadata:Ontologies Data repositories:PhysioNet, CAPdb, CVRG, .. APIs, webservices Validation,Limitations(Journal review) Metadata:Ontologies GO, FMA, .. Model standards: SBML, CellML, FieldML CurationAnnotation Need modules! Model repositories:Biomodels,PMR2 Referencedescription APIs, webservices Functional curation Simulation standards: SED-ML Software:OpenCOR, OpenCMISS, Continuity, Chaste, .. Verification, Benchmarks
Workflow for reference description MICEE etc CellML, SBML& FieldML Specification of models & solution techniques Modelsfromrepository Codes:Simulation Visualisation Comparison with reference data SED-ML Benchmarks PopulationAtlas (Cardiac, MSK, ..) Data:Initial conditionsBoundary conditions Quality control? BioSignalML, DICOM
Physiome Projects EU ProjectsCall 2NoEeuHeartCall 4 MSV (Multi-Scale Visualisation)Ricordo VPH-Share Call 9 TPR (Topological Physiology Resource)OpenMOD • NIHCAP (Cardiac Atlas Project) …
The challenge: organs to proteins Environment Organism Organ system Organ Heart Lungs Diaphragm Knee Colon Liver Eye x 1million 20 generations Tissue Cell Network Cardiac sheets Acinus Osteon Lymph node Liver lobule Nephron Protein Gene Atom
Infrastructure for linking Molecular Biology to Physiome MolecularBiology Cell function Cell process CellMLlibrary Model componentsannotated againstontologies PhysiomeFieldMLlibrary Cell cycle Intracellular signalling Meiosis miRNA GenesmRNA… Proteins Sequence Structure PTMs Binding motifs… Lipids … Carbo-hydrates … Structure & physics Tissue types Cell types Calcium transport Mitosis Protein trafficking Cellreceptors Apoptosis Protein degradation Growth Signallingmodules Electro-physiology Motility Ionchannels Cellular metabolism Contraction Protein synthesis Signalling Metabolicmodules Protein regulation Transport Genenetworks Gene regulation Adhesion Gene transcription … ECM proteinsynthesis
We need (and are well on the way to having): • Model & data encoding standards • Public repositories of curated, annotated & validated models • Reference descriptions of models • Multi-scale, multi-physics algorithms • Carefully managed, open source codes • Benchmark problems • Population atlases
We need (but have only just started): • Better model reduction algorithms • Better ways of handling multi-scale (as opposed to multiple-scale) • 3D cell models • A comprehensive modelling framework for metabolic pathways • A comprehensive modellingframework for signalling pathways • Better links to bioinformaticdatabases • Better links to medical informatics