INTERNET-BASED SOFTWARE FOR MODELING BIOLOGICAL SYSTEMS

IBI’s product offering, ProcessDB, helps molecular cell biologists manage and test their increasingly complex mechanistic hypotheses. ProcessDB does this with a bio-savvy graphical user interface that helps users formulate, visualize, compare, modify, manage and test their own mechanistic theories of cellular function. All models in ProcessDB can be automatically combined with user-specified experimental protocols. Models and their experiments can then be simulated using our integrated solver for testing against experimental data.

ProcessDB version 5.0, released in 2014, is a major upgrade from version 4. The most significant change is the increased speed of the data transfer between the application on your desktop and our central database server. This is particularly noticeable to our clients in countries outside of the US. We have also made improvements to our solver interface.

ProcessDB version 8.0, released in 2020, introduces a host of new tools and improvements, including curation of model processes and molecules by linking them to curated international databases, such as ChEBI, UniProt, BRENDA, and SABIO-RK. We’ve also updated the automatic process that converts diagrams to quantitative models so that it handles even more special cases. New organization and visualization tools have been added to our Graphs pages to support work with ever-more-complex biological models.

The universal medium widely used by biologists to communicate their theories and hypotheses is the scientific diagram or map. ProcessDB uses such diagrams as the main interface between users and their models. Diagrams are automatically converted to working differential equation models based on basic biological and physical principles, but users can always view or modify the resulting equations.

Because model testing requires comparison of model predictions with experimental data, we need to be able to run any experiment on the model being tested. ProcessDB allows you to define as many experiments as you like, and run them on your model so that the model’s predictions for that experiment can be compared directly to the corresponding experimental data. This feature is also useful in experimental design because you can see what your current theory predicts before you do the experiment.

These features require numerical solution of the model equations for one or more experimental designs. So, we need a numerical solver. The ProcessDB solver, implemented by our friends at InSilica Labs, is an extremely fast version of the famous CVODE ordinary differential equation solver. Solver output is displayed in a flexible graphing interface that allows any model variable to be plotted and compared to experimental data. Modelers will be happy to learn that we have also implemented the new and already popular “particle swarm” algorithm for searching parameter space during least squares parameter optimization. Particle swarm searching was designed to find global minima in least squares space. It is resistant to being trapped in a local minimum and thus finds better solutions to complex multiparameter optimization problems.

ProcessDB allows investigators to know with precision what their theories predict, and speeds discovery of mechanisms that account for all of the available data. ProcessDB, which is accessable from any Internet-connected computer, offers a highly secure and professionally-maintained tool that supports mechanistic knowledge management for research laboratories working on complex biological or biomedical problems.

OVERVIEW OF ProcessDB DOCUMENTATION

To find out more about ProcessDB and the modeling of biological systems, the following information is available:

ProcessDB Wiki: this is the most current version of the ProcessDB user guide. It is continually updated as we add new features to the software.

Computational Cell Biology Textbook: This online textbook, written by Robert Phair, can be used by advanced undergraduate and graduate students and professionals in the biomedical sciences or in biomedical engineering who want to use modern computer modeling approaches to test theories against experimental data. The textbook is focused on practical applications; it is a handbook, a guidebook, and a map for the process of formulating and testing biological models. The reader will learn a step-by-step method, applicable to a wide range of biological problems. Early versions of the book were used to teach Dr. Phair’s course, Practical Kinetic Modeling of Biological Systems, when he was a professor in the Department of Physiology and, later, in the Department of Biomedical Engineering, at The Johns Hopkins School of Medicine.