Modular Modeling

Biological models can quickly become as complex as the systems they represent. And minor changes can necessitate a complete rewrite of the model. But researchers may soon snap their models together like LEGOs, using a new programming language called Little b, which uses modularity to simplify biological modeling. Eventually, the authors hope to turn Little b into an easy-to-use tool for biology labs.Little b is based on a core language, which includes the Lisp language it was created in (green) and the knowledge base, symbolic mathematics and syntax modules that allow Little b to reason about biological systems. It also includes modular libraries that describe specific biological interactions, and transla- tors that can generate code used in simulations. Blue areas exist within the current framework; yellow areas are currently under development or are envi- sioned for future work. Reprinted with permission from Mallavarapu, A, et al., Programming with mod- els: modularity and abstraction provide powerful capabilities for systems biology, Journal of the Royal Society Interface, online publication, July 23, 2008.


“I think that as an everyday tool, it [Little b] is going to be kind of like the microscope,” says Aneil Mallavarapu, PhD, lead developer of Little b and a senior research scientist in systems biology at Harvard Medical School. “We’re essentially building a new kind of gel, a new type of microscope for the lab.” The work appears in the June 2008 issue of the Journal of the Royal Society Interface.Biologists traditionally create models to describe unique systems, such as the development of fruit fly embryos or the actions of a phosphorylation cascade on gene transcription. Such computational models are usually based on lists of the system’s properties, which detail every molecular interaction in the system. This allows researchers to tailor models to the precise questions being asked, but it also constrains the model’s usefulness, because it can only probe into one area.


Little b strives to break down biological systems into modules that can be used regardless of the specific context, such as “nuclear export“ or “membrane localization.“ It then defines those parts in a mathematical language. Researchers can use Little b to put together assorted modules to describe their system; Little b then uses those symbolic modules to write out executable code that a scientist could use in a simulation program like MATLAB. “I’ve given Little b the power to reason about biological objects,” Mallavarapu says.


Mallavarapu is excited about the possible use biologists might make of Little b. He would like to see the language help uncover the complex pathways involved in diseases. He hopes that researchers will eventually build entire virtual cells or virtual plants collaboratively, increasing their ability to study their projects in silico.


While the idea of breaking down biological systems into modular chunks may seem logical, Little b may not arrive in the lab immediately, says Birgit Schoeberl, PhD, a senior director of research at Merrimack Pharmaceuticals, Inc, in Cambridge, Massachusetts. “I’m excited about the concept and what I see, but in my own experience, it isn’t straightforward,” Schoeberl says. “I think it’s not quite ready for non-developers. I hope he keeps developing it, or someone takes it on to keep working on the idea.”

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