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

Abstract

For many cell-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 and look at entities and activities that contributed to the development of a simulation model. Therefore, we exploit the PROV Data Model (PROV-DM) and, building on previous work, continue developing a PROV ontology for simulation models. Based on a concrete 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 of individual simulation studies and relate these forming a family of models. The approach is implemented in WebProv, which allows one to insert and query 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 Simulation Models is small. Making these aspects of developing a model explicit and queryable is a crucial step for assessing and reusing simulation models more effectively. The unambiguous specification of information helps to integrate a new simulation model within the family of existing ones. Our approach opens up a wealth of knowledge that may lead to the development of more robust and valid simulation models. We hope that it becomes part of a standardization effort and that modelers adopt the benefits of provenance when considering or creating simulation models.

Receptor/Raft Ratio Is a Determinant for LRP6 Phosphorylation and WNT/β-Catenin Signaling

“…The entities can be found in our git repository 1 https://git.informatik.uni-rostock.de/mosi/receptor-raft-ratio-model. The provenance graph also illuminates the relation to the earlier simulation study(Haack et al, 2015) (for more detailed provenance of this and other WNT signaling models seeBudde et al, 2021).…”