Relating simulation studies by provenance-Developing a family of Wnt signaling models

PLoS Comput Biol. 2021 Aug 5;17(8):e1009227. doi: 10.1371/journal.pcbi.1009227. eCollection 2021 Aug.

Abstract

For many biological systems, a variety of simulation models exist. A new simulation model is rarely developed from scratch, but rather revises and extends an existing one. A key challenge, however, is to decide which model might be an appropriate starting point for a particular problem and why. To answer this question, we need to identify entities and activities that contributed to the development of a simulation model. Therefore, we exploit the provenance data model, PROV-DM, of the World Wide Web Consortium and, building on previous work, continue developing a PROV ontology for simulation studies. Based on a case study of 19 Wnt/β-catenin signaling models, we identify crucial entities and activities as well as useful metadata to both capture the provenance information from individual simulation studies and relate these forming a family of models. The approach is implemented in WebProv, a web application for inserting and querying provenance information. Our specialization of PROV-DM contains the entities Research Question, Assumption, Requirement, Qualitative Model, Simulation Model, Simulation Experiment, Simulation Data, and Wet-lab Data as well as activities referring to building, calibrating, validating, and analyzing a simulation model. We show that most Wnt simulation models are connected to other Wnt models by using (parts of) these models. However, the overlap, especially regarding the Wet-lab Data used for calibration or validation of the models is small. Making these aspects of developing a model explicit and queryable is an important step for assessing and reusing simulation models more effectively. Exposing this information helps to integrate a new simulation model within a family of existing ones and may lead to the development of more robust and valid simulation models. We hope that our approach becomes part of a standardization effort and that modelers adopt the benefits of provenance when considering or creating simulation models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biochemical Phenomena
  • Computational Biology
  • Computer Graphics
  • Computer Simulation
  • Humans
  • Models, Biological*
  • Software
  • Systems Biology
  • Wnt Signaling Pathway*

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (Grant no. SFB 1270/1—299150580: K.B., F.H.; Grant no. 320435134: P.W.) and by the Deutscher Akademischer Austauschdienst (German Academic Exchange Service) through the Research Internships in Science and Engineering (RISE) program (Grant no. 57467143: J.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.