Maurice WilkinsCentre

CellML Workshop 2012

Overview of recent developments in the VPH/Physiome project

15 years of development ..

1999 Systems Biology Markup Language

2006 STEP: Strategy for European Physiome2008 VPH Network of Excellence

2011 VPH Institute

2010 Drug Disease Model Resources (DDMoRe)

1997 IUPS Physiome Committee

1998 CellML, FieldML

2003 IMAG (NIH, NSF, FDA, NASA, DOE, DOD, ..)

Verification, Benchmarks

Experimental measurements

Model standards: SBML, CellML, FieldML

Model repositories: Biomodels, PMR2

Data standards: DICOM, BioSignalML, ..

Minimum information standards: MIAME, MICEE, ..

Data repositories: PhysioNet, CAPdb, CVRG, ..

Standards for models, data & software

Validation,Limitations

(Journal review)

APIs, webservices

Software: OpenCOR, OpenCMISS, Continuity, Chaste, ..

Simulation standards: SED-MLFunctional curation

APIs, webservices

CurationAnnotation

Referencedescription

Metadata:Ontologies

Need modules!

Metadata:OntologiesGO, FMA, ..

Data:Initial conditions

Boundary conditions

PopulationAtlas

(Cardiac, MSK, ..)

Codes:Simulation

Visualisation

Specification of models & solution

techniques

Modelsfrom

repository

SED-ML

BioSignalML, DICOM

Comparison with reference

data

Workflow for reference description

Benchmarks

Quality control?

MICEE etc

CellML, SBML& FieldML

EU Projects Call 2 NoE

euHeart Call 4 MSV (Multi-Scale Visualisation)

RicordoVPH-Share

Call 9 TPR (Topological Physiology Resource)OpenMOD

NIH CAP (Cardiac Atlas Project)…

Physiome Projects

Tissue

Osteon NephronAcinus Liver lobuleLymph nodeCardiac sheets

Organ

Heart Lungs Diaphragm Colon EyeKnee Liver

Environment

Organ systemOrganism

Cell

ProteinGeneAtom

Network

x 1million 20 generations

The challenge: organs to proteins

Motility

Meiosis

Mitosis

Apoptosis

Contraction

Signalling

Transport

Growth

Adhesion

ECM proteinsynthesis

Cell function

Protein degradation

Cell cycle

Protein trafficking

Calcium transport

Intracellular signalling

Gene transcription

Gene regulation

Protein regulation

Protein synthesis

Cellular metabolism

Electro-physiology

Cell process MolecularBiology

miRNAGenesmRNA

…Proteins

SequenceStructure

PTMsBinding motifs

…Lipids

…Carbo-

hydrates…

CellML library

Model componentsannotated against

ontologies

Genenetworks

Metabolicmodules

Ionchannels

Signallingmodules

Cellreceptors

…

PhysiomeFieldMLlibrary

Stru

ctur

e &

phy

sics

Cell

type

s

Tiss

ue ty

pes

Infrastructure for linking Molecular Biology to Physiome

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 modelling

framework for signalling pathways• Better links to bioinformatic databases• Better links to medical informatics

Thanks Andre!