Bio-Logic Builder: A Non-Technical Tool for Building Dynamical, Qualitative Models

Abstract

Computational modeling of biological processes is a promising tool in biomedical research. While a large part of its potential lies in the ability to integrate it with laboratory research, modeling currently generally requires a high degree of training in mathematics and/or computer science. To help address this issue, we have developed a web-based tool, Bio-Logic Builder, that enables laboratory scientists to define mathematical representations (based on a discrete formalism) of biological regulatory mechanisms in a modular and non-technical fashion. As part of the user interface, generalized “bio-logic” modules have been defined to provide users with the building blocks for many biological processes. To build/modify computational models, experimentalists provide purely qualitative information about a particular regulatory mechanisms as is generally found in the laboratory. The Bio-Logic Builder subsequently converts the provided information into a mathematical representation described with Boolean expressions/rules. We used this tool to build a number of dynamical models, including a 130-protein large-scale model of signal transduction with over 800 interactions, influenza A replication cycle with 127 species and 200+ interactions, and mammalian and budding yeast cell cycles. We also show that any and all qualitative regulatory mechanisms can be built using this tool.

Multi-level Modeling of Light-Induced Stomatal Opening Offers New Insights into Its Regulation by Drought

“…The multiple activity levels of the components and the detailed updating functions offer a biologically more accurate representation of the system than Boolean models; for example, the output node, stomatal opening, has more than 20 levels in the model, ranging from 0 to 14.2. The model has a repertoire of more than 10 31 distinct states (see Text S1), which gives it substantial dynamic richness and makes it one of the most complex dynamic models of biological systems (see also [23]–[26]). At the same time the discreteness of the states maintains the computational simplicity of the model.…”

A Comprehensive, Multi-Scale Dynamical Model of ErbB Receptor Signal Transduction in Human Mammary Epithelial Cells

“…The construction of the model was accomplished using The Cell Collective (www.thecellcollective.org; [32]), a collaborative modeling platform for large-scale biological systems. The platform allows users to construct and simulate large-scale computational models of various biological processes based on qualitative interaction information using the platform's Bio-Logic Builder which converts the entered qualitative biochemical information into Boolean expressions in the background [47]. (Though the Boolean expressions for any model created in the platform can be downloaded from the website.)…”

Using computational modeling to teach metabolism as a dynamic system improves student performance

“…Each component can represent a variety of elements ranging from a single enzyme or metabolite to an entire process, depending on the scope of the model and the level of abstraction. The directed edges correspond to biochemical interactions (direct or indirect) among the components (e.g., Glucose-6-phosphate activates Glucose-6-phosphate dehydrogenase IF/WHEN NAD+ is active) (50). The activity of a component is determined by its regulatory mechanism, reflecting the activity of other directly interacting components.…”