Rule-Based Modeling of Biochemical Systems

The use of rules to represent and simulate the interactions of molecules in biochemical regulatory networks [1] is an emerging area of systems biology that promises to change the way these networks are modeled and understood. The purpose of this proposed workshop is to bring together representatives from major research groups active in this area for the purpose of exchanging ideas, discussing applications of rule-based modeling methods, surveying existing capabilities, mapping out where the field is headed, and developing standards that will promote the exchange of models and the development of new software tools. As part of this, one pratical goal will be to discuss and (hopefully) settle on a draft proposal for representing multicomponent species and complexes within the framework of SBML.

Workshop Organization

The workshop organizers are:

• Jim Faeder (Theoretical Biology and Biophysics Group, LANL)
• Bill Hlavacek (Center for Nonlinear Studies, LANL)
• Walter Fontana (Department of Systems Biology, Harvard Medical School)
• Michael Hucka (Caltech)

This workshop is made possible thanks to generous support from the following organizations:

• The Santa Fe Institute
• Center for Nonlinear Studies, Los Alamos National Laboratory
• Beckman Institute BNMC at Caltech

Preliminary Workshop Schedule and Venue Information

All talks will be 25 minutes followed by 5 minutes for questions.

Wednesday, June 13

6:00-? PM Welcome reception at the Hotel Santa Fe.

Thursday, June 14

8:30-8:40 Opening Remarks

8:40-9:10 William Hlavacek (LANL) An Overview of Rule-Based Modeling

Software for Rule-Based Modeling

The objective for this session is to provide an overview of the tools available for rule-based modeling. Key questions for the speakers to address are 1) What biological features and questions motivated the development of the software? 2) What capabilities does the software provide? 3) What are specific examples where the approach/software have led to new insights? 4) What capabilities still need to be developed? 5) What are the essential entities and processes that you feel must be represented in any exchange format to support your modeling needs and software?

9:10-9:40 James Faeder (LANL) BioNetGen

9:40-10:10 Larry Lok (MSI) Moleculizer

10:10-10:40 Coffee Break Sponsored by SFI

10:40-11:10 Martin Meier-Schellersheim (NIH/NIAID) Simmune

11:10-11:40 Anika Öllrich (EBI) StochSim

11:40-12:10 Aneil Mallavarapu Little b

12:10-1:30 PM Catered Lunch Sponsored by SFI

1:30-2:00 PM Pat Lincoln (SRI) Pathway Logic

2:00-2:30 PM Ozan Kahramano On Concurrent Computations in Petri Nets for Modelling Signalling Pathways

2:30-3:00 PM Ricardo Paxson (Mathworks) Introduction to SimBiology and possible future enhancements for rule based modeling

3:00-3:30 PM Coffee Break Sponsored by SFI

Representational Issues in Rule-Based Modeling

3:30-4:00 PM Sohyoung Kim (NIH/NCI) Depicting combinatorial complexity with the molecular interaction map notation

4:00-4:30 PM Stephen Racunas (Penn State) Representation and Evaluation of Biochemical Hypotheses

4:30-5:00 PM Ty Thomson (MIT) A Collaborative Process for Building and Documenting Biological Models

5:00-5:30 PM Jean Krivine (École Polytechnique) TBA

5:30-5:45 PM Day 1 Summary and Thoughts About Day 2 (Hucka)

6:30 PM Dinner at Ristra Sponsored by SFI

Friday, June 15

Applications and Computational Aspects

8:30-9:00 Vincent Danos (CNRS) What is so special about biological signalling?

9:00-9:30 Holger Conzelmann (University of Stuttgart) Signal transduction and combinatorial complexity: Model reduction, reduced modeling and thermodynamic constraints

9:30-10:00 Richard G. Posner (TGen) Mechanistic modeling of signaling pathways

10:00-10:30 Coffee Break Sponsored by SFI

10:30-11:00 Will Chen (Harvard) Phospho-dynamic Experiments and Computational Modeling of the ErbB Pathways

Towards Standards for Rule-Based Modeling

11:00-11:30 Michael Hucka (Caltech) An Overview of SBML and Goals for SBML Level 3

11:30-12:00 Nathan Addy (MSI) Experiences Converting Between BNG and Moleculizer Input Formats

12:00-1:30 PM Lunch Sponsored by SFI

1:30-2:00 PM Michael Blinov (UCHC) TBA

2:00-2:30 PM Emek Demir (MSKCC) Rule based aspects in BioPAX

Open Discussion of SBML Level 3 Proposals

2:30-3:30 PM Presentation of SBML Level 3 Proposal (Blinov) Followed by Discussion

3:30-4:00 PM Coffee Break Sponsored by SFI

4:00-? PM Open Discussion about Level 3 and Other Topics in Rule-Based Modeling. Preparation of a conference report to be submitted to Molecular Systems Biology. Future meetings?

Saturday, June 16

Morning Departure

Recommended Background Readings

If you have time for nothing else, we strongly recommend reading the following before coming to the meeting:

• Hlavacek WS, Faeder JR, Blinov ML, Posner RG, Hucka M, Fontana W, Rules for modeling signal-transduction systems, Science STKE, 18 July 2006 PDF. This is a a comprehensive review of rule-based modeling written by the organizers.

• Kohn, KW, Aladjem, MI, Kim, S, Weinstein, JN, Pommier, Y "Depicting combinatorial complexity with the molecular interaction map notation" Mol Syst Biol 2006 PubMed Abstract

The following are important for the discussions about extending SBML to support this class of modeling:

• Michael Blinov et al.'s 2004 proposal for SBML Level 3 extensions for multicomponent species PDF
• Andrew Finney's 2004 proposal for SBML Level 3 extensions for multicomponent species PDF
• The SBML Level 2 Version 3 public prerelease specification PDF

Additional readings for context and background (speakers - please suggest a paper, ideally current and technically detailed):

• Blinov, Yang, Faeder & Hlavacek, "Graph theory for rule-based modeling of biochemical networks," Lect. Notes Comput. Sci. 4230, 89-106 [2]
• Lok & Brent, "Automatic generation of cellular reaction networks with Moleculizer 1.0", Nat. Biotech. 23(1):131-136, 2005. PDF

Travel Information

The Santa Fe Institute is located in Santa Fe, a small town in New Mexico, USA.

• Link to Google map showing the SFI and the hotel
• GIF image of a map showing the SFI and the rest of Santa Fe
• Live weather forecast for Santa Fe

To get to the Santa Fe Institute from outside of New Mexico, you will most likely be flying into Albuquerque International Airport (code: ABQ), which is 60 miles (~100km) away from Santa Fe. It is also possible, though unlikely, that you will fly into the Santa Fe Municipal Airport (code: SAF), but few airlines make connections there. The Santa Fe Institute provides the following useful pages of information about transportation to SFI from ABQ:

• Ground transportation options from ABQ to Santa Fe
• Driving to the Hotel Santa Fe from ABQ
• Driving to SFI from ABQ

The following are some suggestions and recommendations for international visitors:

• Distances in the western USA are deceptively long (much longer than you may expect from driving in other areas of the world) and the region is sparsely populated. If you are planning on doing any sightseeing, make sure to check your distances carefully.
• English is the dominant language in Santa Fe. Many residents also speak Spanish.
• Airport currency exchange services are usually more expensive than taking cash out of an ATM or exchanging at a bank. You may want to check the current exchange rates (e.g., at xe.com) so that you have some idea of what to expect, although of course you will not get the exact exchange rate because all services charge a percentage for doing the exchange.
• Tipping is customary in the USA and generally not precomputed on bills. 15%-20% is typical and expected for restaurants and taxis, tipping $2-$5 if someone carries your bags or parks your car is also typical, and leaving $2 for the hotel room cleaning staff every day is also appreciated by the staff.
• You may wish to obtain whatever kind of power adapter is necessary for you to use your laptop and other electrical devices before you arrive into Santa Fe. It may be possible to buy converters at shops around your hotel or elsewhere in Santa Fe, but it is not guaranteed, nor is it assured they will have the right type for your electrical needs. See [3] for information about electric standards in the USA.