LM-Merger: a workflow for merging logical models with an application to gene regulatory network models

Abstract Background Gene regulatory network (GRN) models provide mechanistic understanding of genetic interactions that regulate gene expression and, consequently, influence cellular behavior. Dysregulated gene expression plays a critical role in disease progression and treatment response, making GR...

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Main Authors: Luna Xingyu Li, Boris Aguilar, John Gennari, Guangrong Qin
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Bioinformatics
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Online Access:https://doi.org/10.1186/s12859-025-06212-2
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author Luna Xingyu Li
Boris Aguilar
John Gennari
Guangrong Qin
author_facet Luna Xingyu Li
Boris Aguilar
John Gennari
Guangrong Qin
author_sort Luna Xingyu Li
collection DOAJ
description Abstract Background Gene regulatory network (GRN) models provide mechanistic understanding of genetic interactions that regulate gene expression and, consequently, influence cellular behavior. Dysregulated gene expression plays a critical role in disease progression and treatment response, making GRN models a promising tool for precision medicine. While researchers have built many models to describe specific subsets of gene interactions, more comprehensive models that cover a broader range of genes are challenging to build. This necessitates the development of approaches for improving the models through model merging. Results We present LM-Merger, a workflow for semi-automatically merging logical GRN models. The workflow consists of five main steps: (a) model identification, (b) model standardization and annotation, (c) model verification, (d) model merging, and (e) model evaluation. We demonstrate the feasibility and benefit of this workflow with two pairs of published models pertaining to acute myeloid leukemia (AML). The integrated models were able to retain the predictive accuracy of the original models, while expanding coverage of the biological system. Notably, when applied to a new dataset, the integrated models outperformed the individual models in predicting patient response. Conclusions This study highlights the potential of logical model merging to advance systems biology research and our understanding of complex diseases. By enabling the construction of more comprehensive models, LM-Merger facilitates deeper insights into disease mechanisms and enhances predictive modeling for precision medicine applications. Clinical trial number Not applicable.
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spelling doaj-art-d91b9247b9b6487d854e7607c460c1d92025-08-20T03:46:15ZengBMCBMC Bioinformatics1471-21052025-07-0126111510.1186/s12859-025-06212-2LM-Merger: a workflow for merging logical models with an application to gene regulatory network modelsLuna Xingyu Li0Boris Aguilar1John Gennari2Guangrong Qin3Institute for Systems BiologyInstitute for Systems BiologyDepartment of Biomedical Informatics and Medical Education, University of WashingtonInstitute for Systems BiologyAbstract Background Gene regulatory network (GRN) models provide mechanistic understanding of genetic interactions that regulate gene expression and, consequently, influence cellular behavior. Dysregulated gene expression plays a critical role in disease progression and treatment response, making GRN models a promising tool for precision medicine. While researchers have built many models to describe specific subsets of gene interactions, more comprehensive models that cover a broader range of genes are challenging to build. This necessitates the development of approaches for improving the models through model merging. Results We present LM-Merger, a workflow for semi-automatically merging logical GRN models. The workflow consists of five main steps: (a) model identification, (b) model standardization and annotation, (c) model verification, (d) model merging, and (e) model evaluation. We demonstrate the feasibility and benefit of this workflow with two pairs of published models pertaining to acute myeloid leukemia (AML). The integrated models were able to retain the predictive accuracy of the original models, while expanding coverage of the biological system. Notably, when applied to a new dataset, the integrated models outperformed the individual models in predicting patient response. Conclusions This study highlights the potential of logical model merging to advance systems biology research and our understanding of complex diseases. By enabling the construction of more comprehensive models, LM-Merger facilitates deeper insights into disease mechanisms and enhances predictive modeling for precision medicine applications. Clinical trial number Not applicable.https://doi.org/10.1186/s12859-025-06212-2Gene regulatory networksLogical modelsModel integrationAcute myeloid leukemiaSystems biology
spellingShingle Luna Xingyu Li
Boris Aguilar
John Gennari
Guangrong Qin
LM-Merger: a workflow for merging logical models with an application to gene regulatory network models
BMC Bioinformatics
Gene regulatory networks
Logical models
Model integration
Acute myeloid leukemia
Systems biology
title LM-Merger: a workflow for merging logical models with an application to gene regulatory network models
title_full LM-Merger: a workflow for merging logical models with an application to gene regulatory network models
title_fullStr LM-Merger: a workflow for merging logical models with an application to gene regulatory network models
title_full_unstemmed LM-Merger: a workflow for merging logical models with an application to gene regulatory network models
title_short LM-Merger: a workflow for merging logical models with an application to gene regulatory network models
title_sort lm merger a workflow for merging logical models with an application to gene regulatory network models
topic Gene regulatory networks
Logical models
Model integration
Acute myeloid leukemia
Systems biology
url https://doi.org/10.1186/s12859-025-06212-2
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