Multiscale Systems Biology WG Breakout session Sept. 3, 2014

Some past MSB-WG webinars: Heterogeneous Model Composability: Another Step Toward Scientifically Useful Multiscale Models Hessam Sarjoughian, Anthony Hunt, Jennifer Linderman May 14, Biocellion: Accelerating Computer Simulation of Multicellular Biological System Models Seunghwa Kang, Nick Flann, Simon Kahan, Ilya Shmulevich, March 11, Multiscale Molecular Systems Biology: Reconstruction and Model Optimization Ronan Fleming, August 16, 2013 The virtual liver: towards quantitative modeling of liver regeneration Dr. Dirk Drasdo, March 21, 2013.

Some (common) themes emerged in discussion: Modularity Model sharing Reproducibility (models vs. experiments)

Modularity (intro by Dan Beard) Biological modularity is different from software engineering “White box modularity”, semi-automated merging of modules e.g. bioreceptor with cardiac dynamics Joining models by establishing equivalence relations between variables or parameters in different modules What is the minimal specification that should be required to enable shared modules to be integrated? (A. Popel) Isolated cell might not operate like the same cell in the body - limit to modularity (Meyer Katzper)

Model Sharing / Standards Need standards for how to annotate what is in the model, use of common ontology, not two ontologies for the same thing, standards for annotation (DB) Each module has its own assumptions, parameters, variables, etc., how to join models together in such a circumstance? (Ashley Kia) Journals do in principle agree on the need for standards, but don't want to create barriers to submission (DB) CellML, SBML - strict in certain domains, but in multiscale models of physiology, the standards are yet to be set, but we still need annotation of what exists to allow interoperability (DB) Challenge: getting into and out of a standard format, e.g. when code written in Fortran or C for high performance, how to get it into standard format (Moshin) Password controlled access to code in order to count the number of users to then report to funding agencies. journals could collect download statistics (A. Popel) Need for a repository of models that can't adhere to standards that exist (M. King) Movement in publishing on experimental side to share protocols but no comparitive protocol journal for computational modeling (MK)

Model Sharing / Standards (part 2) Released code must be more robust - in house use to released code takes a lot of effort - need to guard against spurious conclusions obtained from improper use. (Anon) Fear of sharing: sharing code to everybody might make a researcher redundant, no problem to share with collaborators (Anon) Sharing of models distinct from sharing of code, code does not contain the model, it runs the model (A. McCulloch) Separation of simulation code (available as compiled program) from model specification code (completely open) (AM) Workflow is an important part to be shared (e.g. for combining pde simulation with machine learning, sensitivity analysis etc) (AM) Standards often lag behind aspects being represented in models being currently developed (Gary An) Are models reagents or tools? (comparison with experimental sharing) J. Linderman, F. MacCabhann, I. Melas Different compilers can give different results (Meyer Katzper) How to collect remote usage statistics (R. Fleming)

Reproducibility In general the publication is insufficient to reproduce the modeling (DB) Some models cannot be specified mathematically, so how can it be reproduced without the original code? (DB) We must strive to make our modeling reproducible - reproducibility is one of the cornerstones of science (Tony Hunt) What is the scientific value of a modeling publication that takes years to reproduce (due to lack of specification) (TH) Almost impossible to reproduce a paper with description given in the majority of papers (Moshin) Provision of sufficient material to reproduce the modeling results (A. Popel) What constitutes sufficient specification to reproduce modeling result without the actual source code? published wet-lab protocols often not sufficient to experiments (Gary An)

Transitioning WB co-leads Past/current Co-leads: Dan Beard, Mike King, Sasha Popel New Co-leads: Ronan Fleming (U. Luxembourg) Volunteers / new awardees are welcome to get involved!