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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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| 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. |
| format | Article |
| id | doaj-art-d91b9247b9b6487d854e7607c460c1d9 |
| institution | Kabale University |
| issn | 1471-2105 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| 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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