A framework for exhaustive modelling of genetic interaction patterns using Petri nets

Annika Jacobsen; Olga Ivanova; Saman Amini; Jaap Heringa; Patrick Kemmeren; K Anton Feenstra

doi:10.1093/bioinformatics/btz917

A framework for exhaustive modelling of genetic interaction patterns using Petri nets

Annika Jacobsen, Olga Ivanova, Saman Amini, Jaap Heringa, Patrick Kemmeren, K Anton Feenstra^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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Abstract

MOTIVATION: Genetic interaction (GI) patterns are characterized by the phenotypes of interacting single and double mutated gene pairs. Uncovering the regulatory mechanisms of GIs would provide a better understanding of their role in biological processes, diseases, and drug response. Computational analyses can provide insights into the underpinning mechanisms of GIs.

RESULTS: In this study, we present a framework for exhaustive modelling of GI patterns using Petri nets (PN). Four-node models were defined and generated on three levels with restrictions, to enable an exhaustive approach. Simulations suggest ∼5 million models of GIs. Generalizing these we propose putative mechanisms for the GI patterns, inversion and suppression. We demonstrate that exhaustive PN modelling enables reasoning about mechanisms of GIs when only the phenotypes of gene pairs are known. The framework can be applied to other GI or genetic regulatory datasets.

AVAILABILITY: The framework is available at http://www.ibi.vu.nl/programs/ExhMod.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Original language	English
Pages (from-to)	2142-2149
Number of pages	8
Journal	Bioinformatics
Volume	36
Issue number	7
Early online date	17 Dec 2019
DOIs	https://doi.org/10.1093/bioinformatics/btz917
Publication status	Published - 1 Apr 2020

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abstract = "MOTIVATION: Genetic interaction (GI) patterns are characterized by the phenotypes of interacting single and double mutated gene pairs. Uncovering the regulatory mechanisms of GIs would provide a better understanding of their role in biological processes, diseases, and drug response. Computational analyses can provide insights into the underpinning mechanisms of GIs.RESULTS: In this study, we present a framework for exhaustive modelling of GI patterns using Petri nets (PN). Four-node models were defined and generated on three levels with restrictions, to enable an exhaustive approach. Simulations suggest ∼5 million models of GIs. Generalizing these we propose putative mechanisms for the GI patterns, inversion and suppression. We demonstrate that exhaustive PN modelling enables reasoning about mechanisms of GIs when only the phenotypes of gene pairs are known. The framework can be applied to other GI or genetic regulatory datasets.AVAILABILITY: The framework is available at http://www.ibi.vu.nl/programs/ExhMod.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.",

author = "Annika Jacobsen and Olga Ivanova and Saman Amini and Jaap Heringa and Patrick Kemmeren and Feenstra, {K Anton}",

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AU - Jacobsen, Annika

AU - Ivanova, Olga

AU - Amini, Saman

AU - Heringa, Jaap

AU - Kemmeren, Patrick

AU - Feenstra, K Anton

PY - 2020/4/1

Y1 - 2020/4/1

N2 - MOTIVATION: Genetic interaction (GI) patterns are characterized by the phenotypes of interacting single and double mutated gene pairs. Uncovering the regulatory mechanisms of GIs would provide a better understanding of their role in biological processes, diseases, and drug response. Computational analyses can provide insights into the underpinning mechanisms of GIs.RESULTS: In this study, we present a framework for exhaustive modelling of GI patterns using Petri nets (PN). Four-node models were defined and generated on three levels with restrictions, to enable an exhaustive approach. Simulations suggest ∼5 million models of GIs. Generalizing these we propose putative mechanisms for the GI patterns, inversion and suppression. We demonstrate that exhaustive PN modelling enables reasoning about mechanisms of GIs when only the phenotypes of gene pairs are known. The framework can be applied to other GI or genetic regulatory datasets.AVAILABILITY: The framework is available at http://www.ibi.vu.nl/programs/ExhMod.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

AB - MOTIVATION: Genetic interaction (GI) patterns are characterized by the phenotypes of interacting single and double mutated gene pairs. Uncovering the regulatory mechanisms of GIs would provide a better understanding of their role in biological processes, diseases, and drug response. Computational analyses can provide insights into the underpinning mechanisms of GIs.RESULTS: In this study, we present a framework for exhaustive modelling of GI patterns using Petri nets (PN). Four-node models were defined and generated on three levels with restrictions, to enable an exhaustive approach. Simulations suggest ∼5 million models of GIs. Generalizing these we propose putative mechanisms for the GI patterns, inversion and suppression. We demonstrate that exhaustive PN modelling enables reasoning about mechanisms of GIs when only the phenotypes of gene pairs are known. The framework can be applied to other GI or genetic regulatory datasets.AVAILABILITY: The framework is available at http://www.ibi.vu.nl/programs/ExhMod.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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A framework for exhaustive modelling of genetic interaction patterns using Petri nets

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