MDL Meeting Notes

2002-09-25 and 2002-09-26 at MIT

ParticipantsDrew Endy (MIT), Tom Knight (MIT),

George Church (Harvard), Oleg Sokolsky (UPenn), Daniel Zak (U.Delaware/ThomasJeffferson U),

Birgit Schoeberl (MIT), Jim Collins (B.U.), Jonathan Webb (BBN), Cliff Shaffer (VT),

Peter Finin (UPenn), Michael Hucka (Caltech), Andrew Finney (Caltech), Chris Cox (UTenn), Jesse S.A. Bridgewater (UCLA), Dennis A Dean

(Harvard), Katherine Gurdlier (BMU / Harvard), Jordan Fielder (MITRE), Olivia Tate (MITRE),

David Beckwith (UCLA), Daniel Segre (Harvard), Wayne Rindone (Harvard), Sriram Kosuri (MIT),

Clare Thiem (AFRL), Tom Garvey (SRI), Patrick Lincoln (SRI), Leon Chan (MIT),

Arch Owen (BBN), Bud Misra (NYU)

Summary - Key Talking Points

1. Model Type Examples

2. Model Definition Language Specification, Requirements, & Vocabulary

3. BioSPICE System Integration

How to Get Things Moving Group agreement on deadlines

• Use cases/MDL specification & requirements: – Oct 15 first draft– Halloween draft to MDL group

• Model types:– Halloween 12 different model types

Volunteer to be chief annoying person on model types: Cliff Shaffer

Volunteer to be chief annoying person on use cases/MDL requirements: Patrick Lincoln

Lesson from the Past Model definitions need to support:

• Search – BLAST, etc.

• Merging – Dock two modeled components together

• Checking – Connect with other datatypes, compare independently

generated models

Model Types - Discussion Chemical Kinetic

• Normal (Tyson/Shaffer/Kumar)• Fine-grained (Kosuri/Arkin)• Complexes (Lok/Finney/Faeder)• Markov models (Cox)…abstraction is research

3D• PDE (Arkin/Lowe/Przekwas)• Ray Tracing (Bartol/Stiles)

Flux Balance (Segres) Static Graph (Karp) Boolean/Logic (Lincoln) Bayesian inferred models (Gifford, Liao,

Lauffenberger) Diagramatic notations (Hucka, Schoeberl, Kohn) Other

Model Types - Points of Contact

1. Chemical Kinetics EndyNormal/ODE (Tyson, Others), Fine-grained/Stoch (Cox), Complexes

(Endy)

2. Static / graph / Flux balance Church, Lincoln, Lok?, Hucka

3. Automata (cell movement) Schoeberl, Kaiser4. Markov Cox?5. 2d/3d PDE diffusion Virtual Cell, Finney? 6. S-system (power law format ODE) Mishra 7. Hybrid systems Lincoln, Sokolsky8. 4D: structural/cell dynamics Church9. Boolean, Digital, Discrete event Hucka10. Shape/4d ray trace Endy Mcell?11. Electrophysiology ODE Zak12. Delay differential equations Zak

BioSPICE.org sandbox folders Lincoln

Model Types - By Halloween

1. Chemical Kinetics Endy (SBML)Normal/ODE (Tyson, Others), Fine-grained/Stoch (Cox), complexes (Endy)

2. Static / graph / Flux balance Church, Lincoln, Lok?, Hucka (SMBL)

3. Automata (cell movement) Schoeberl, Kaiser (SBML)4. Markov Beckwith, Cox? (no)5. 2d/3d PDE diffusion Virtual Cell, Arkin, Finney? (no)6. S-system (power law format ODE) Mishra (SBML composition?)7. Hybrid systems Lincoln, Sokolsky (no…?) 8. 4D: structural/cell dynamics Church (no)9. Boolean, Digital, Discrete event Hucka (SBML)10. Shape/4d ray trace Endy, Mcell? (no)11. Electrophysiology ODE Zak (no…VCell?)12. Delay differential equations Zak (SBML)

(SBML) == SBML does/will handle, (no) == SBML does not handle

Working Groups - discussion Existing BioSPICE working groups: DB, EWG, MDL System-level integration (needed now)

• Identify overall map, components that make it up• System-level • Includes communication architecture (APIs)• E.g., “this is the API for a simulator”• Do it by layering, identify common functionality• Extensible interfaces

Model builder GUIs (community exists already) Simulators (community exists already?)

• Multiple simulators operating simultaneously, validation • Have affinity group meeting at Dec 02 PI meeting (Garvey)

Non-simulator analysis tools• Have affinity group meeting at Dec 02 PI meeting (Garvey)

Data modeling (Resources? Do this in future)

BioSPICE Components Model building GUIs

• Reads and writes MDL Analysis tools

• Model analysis – Simulators

• Reads MDL, parameter values, configuration– Bifurcation, reachability, sensitivity analysis, elementary

modes • Data analysis

– Compare experimental data with output of simultators, parameter estimation, confidence

Control systems• Coordinate multiple simulators, multiple models• Version control, multiple runs, Chicago Chimera, make

Databases – connections Lab notebook End-to-end use cases: Hucka

Data Modeling: Added Working Group?

From raw data to mechanism, rate terms and parameter estimates.

Metadata (model points back to dataset)• Version, author, …

Bayesian inference of models

Notes on Model Definition Language Specification, Requirements, & Vocabulary

MDL Discussion -- Cliff’s List What goes in a model definition language

• Metadata scheme• Graphical layout• Geometry / topology • Variables (species, things with names)• Bits of computation

– Named functions for use in rate laws

• States• Control (state transitions, compartment…)• Set of constraints• Objective function

– Might be a bit of computation

What is Needed Need group that looks at components and

how they fit together Interagent coordination language:

• OAA is much improved, particularly performance

Inputs to simulator? But don’t need BioSPICE working groups

when there are already healthy communities • Model building (user interfaces), simulators

Map out the space• What are the gaps?

System integration Overall functionality The art of how they fit together

What MDL is Not Not data model Not process model Not integration language for components Not ontology for biology, biochemistry

• But we will produce a controlled vocabulary• But we may require an ontology

MDL definition Comes from use cases

1. Model development2. Model creation / editing / evolution3. Domain extensibility4. Simulation (numeric)5. Analysis (symbolic)6. Models as a useable tool for browsing, etc

Personal organization

7. Models a presentation or communication mechanismWhiteboard

8. Producing a formal representation is usefulMDL can play a role in that intellectual activity

End of October

MDL Use Cases1. Model development

Model creation

2. AnalysisSymbolic and numeric (Simulation) Model validationWet-lab experiment design

• Models as a useful organization tool for browsing, etcPersonal organization

• Models a presentation or communication mechanismWhiteboard

• Domain extensibilityEditing and evolution of models

• Producing a formal representation is useful in itselfMDL can play a role in that intellectual activity

1. Model discovery (Regulography)

Action Items: First draft Oct 15 Webb and Hucka

• Use case guide and example Shaffer (Full Tyson example) Zak sensitivity analysis, experimental design Bridgewater (Simulation) (coupled

represselators) Dennis (brainstorming, collaboration) Experimental design, model validation (Cox) Model discovery, regulography (Beckwith) Model creation (Finney, Bridgewater) Mode switching, hybrid control need to be in

MDL

Model Development Flow1. Experimental design2. Experimental data processing

Array sw, expression data management3. Identification of players

Genomics sw, clustering sw4. Annotation vis-à-vis known info

Genomic5. Relationship inference

Bayesian6. Generation of qualitative model

Model induction7. Generation of quantitative model

Optimization8. Simulation / analysis / prediction

Matlab, XS, BioReactor, Sensitivity analysis9. Publication of model

Collaboration Diversity of Discipline, Organization,

Location– MDL needs: defined vocabulary, mappings– MDL needs: ability to difference – MDL needs: version control annotation?