Predicting Phenotype from Genotype Through Automatically Composed Petri Nets

TL;DR

This paper introduces a modular, database-driven Petri net framework for modeling gene effects and genotype-phenotype relationships, enabling dynamic updates and community collaboration in complex biological systems.

Contribution

It presents a novel, composable Petri net approach with version control and web interface for modeling gene and mutation effects in a flexible, scalable manner.

Findings

Automated assembly of models considering cell-specific gene expression.

Prediction of pleiotropic effects of gene mutations.

Compatibility of forward and reverse engineered modules.

Abstract

We describe a modular modelling approach permitting curation, updating, and distributed development of modules through joined community effort overcoming the problem of keeping a combinatorially exploding number of monolithic models up to date. For this purpose, the effects of genes and their mutated alleles on downstream components are modeled by composable, metadata-containing Petri net models organized in a database with version control, accessible through a web interface. Gene modules can be coupled to protein modules through mRNA modules by specific interfaces designed for the automatic, database-assisted composition. Automatically assembled executable models may then consider cell type-specific gene expression patterns and the resulting protein concentrations. Gene modules and allelic interference modules may represent effects of gene mutation and predict their pleiotropic consequences or uncover complex genotype/phenotype relationships. Forward and reverse engineered modules are fully compatible.