Maurice Wilkins Centre CellML Workshop 2012 Overview of recent developments in the VPH/Physiome project

15 years of development Systems Biology Markup Language 2006 STEP: Strategy for European Physiome 2008 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-ML Functional curation APIs, webservices Curation Annotation Reference description Metadata: Ontologies Need modules! Metadata: Ontologies GO, FMA,..

Data: Initial conditions Boundary conditions Population Atlas (Cardiac, MSK,..) Codes: Simulation Visualisation Specification of models & solution techniques Models from repository SED-ML BioSignalML, DICOM Comparison with reference data Workflow for reference description Benchmarks Quality control? MICEE etc CellML, SBML & FieldML

EU Projects Call 2NoE euHeart Call 4MSV (Multi-Scale Visualisation) Ricordo VPH-Share Call 9TPR (Topological Physiology Resource) OpenMOD NIHCAP (Cardiac Atlas Project) … Physiome Projects

Tissue OsteonNephronAcinusLiver lobuleLymph nodeCardiac sheets Organ HeartLungsDiaphragmColonEyeKneeLiver Environment Organ system Organism Cell Protein Gene Atom Network x 1million 20 generations The challenge: organs to proteins

Motility Meiosis Mitosis Apoptosis Contraction Signalling Transport Growth Adhesion ECM protein synthesis 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 processMolecular Biology miRNA Genes mRNA … Proteins Sequence Structure PTMs Binding motifs … Lipids … Carbo- hydrates … CellML library Model components annotated against ontologies Gene networks Metabolic modules Ion channels Signalling modules Cell receptors … Physiome FieldML library Structure & physics Cell types Tissue types 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!