4.7 Article

A practical guide to mechanistic systems modeling in biology using a logic-based approach

Journal

BRIEFINGS IN BIOINFORMATICS
Volume 22, Issue 4, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/bib/bbaa236

Keywords

mechanistic logic-based models; in silico simulations; lac operon; computational systems biology; Cell Collective; GINsim

Funding

  1. National Institutes of Health [1R35GM119770-04]

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The passage discusses the use of mechanistic computational models in studying regulatory mechanisms in biological processes, and presents a detailed protocol for model construction. The protocol outlines steps including defining scope, choosing validation criteria, selecting modeling approach, constructing and simulating the model.
Mechanistic computational models enable the study of regulatory mechanisms implicated in various biological processes. These models provide a means to analyze the dynamics of the systems they describe, and to study and interrogate their properties, and provide insights about the emerging behavior of the system in the presence of single or combined perturbations. Aimed at those who are new to computational modeling, we present here a practical hands-on protocol breaking down the process of mechanistic modeling of biological systems in a succession of precise steps. The protocol provides a framework that includes defining the model scope, choosing validation criteria, selecting the appropriate modeling approach, constructing a model and simulating the model. To ensure broad accessibility of the protocol, we use a logical modeling framework, which presents a lower mathematical barrier of entry, and two easy-to-use and popular modeling software tools: Cell Collective and GINsim. The complete modeling workflow is applied to a well-studied and familiar biological process-the lac operon regulatory system. The protocol can be completed by users with little to no prior computational modeling experience approximately within 3 h.

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