Conceptual Model-based Systems Biology: mapping knowledge and discovering gaps in the mRNA transcription cycle

PLoS One. 2012 Dec 20;7(12):e51430. doi: 10.1371/journal.pone.0051430. Epub 2012 Dec 20.

Abstract

We propose a Conceptual Model-based Systems Biology framework for qualitative modeling, executing, and eliciting knowledge gaps in molecular biology systems. The framework is an adaptation of Object-Process Methodology (OPM), a graphical and textual executable modeling language. OPM enables concurrent representation of the system's structure-the objects that comprise the system, and behavior-how processes transform objects over time. Applying a top-down approach of recursively zooming into processes, we model a case in point-the mRNA transcription cycle. Starting with this high level cell function, we model increasingly detailed processes along with participating objects. Our modeling approach is capable of modeling molecular processes such as complex formation, localization and trafficking, molecular binding, enzymatic stimulation, and environmental intervention. At the lowest level, similar to the Gene Ontology, all biological processes boil down to three basic molecular functions: catalysis, binding/dissociation, and transporting. During modeling and execution of the mRNA transcription model, we discovered knowledge gaps, which we present and classify into various types. We also show how model execution enhances a coherent model construction. Identification and pinpointing knowledge gaps is an important feature of the framework, as it suggests where research should focus and whether conjectures about uncertain mechanisms fit into the already verified model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics*
  • Models, Genetic
  • RNA, Messenger / genetics*
  • Systems Biology*
  • Transcription, Genetic*

Substances

  • RNA, Messenger

Grants and funding

This work was funded in part by a grant agreement No. 38221 for Promoting Women in Science by the Israeli Ministry of Science to JS. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 262044 – VISIONAIR and from Gordon Center for Systems Engineering at the Technion. This work was partially supported by a grant from Israel Science Foundation to MC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.