Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns
Abstract Background Ubiquitin ligases (Ub-ligases) are essential intracellular enzymes responsible for the regulation of proteome homeostasis, signaling pathway crosstalk, cell differentiation and stress responses. Individual Ub-ligases exhibit their unique functions based on the nature of their sub...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12876-022-02265-2 |
| _version_ | 1811302151221149696 |
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| author | Veronika Iatsiuk Frantisek Malinka Marketa Pickova Jolana Tureckova Jiri Klema Frantisek Spoutil Vendula Novosadova Jan Prochazka Radislav Sedlacek |
| author_facet | Veronika Iatsiuk Frantisek Malinka Marketa Pickova Jolana Tureckova Jiri Klema Frantisek Spoutil Vendula Novosadova Jan Prochazka Radislav Sedlacek |
| author_sort | Veronika Iatsiuk |
| collection | DOAJ |
| description | Abstract Background Ubiquitin ligases (Ub-ligases) are essential intracellular enzymes responsible for the regulation of proteome homeostasis, signaling pathway crosstalk, cell differentiation and stress responses. Individual Ub-ligases exhibit their unique functions based on the nature of their substrates. They create a complex regulatory network with alternative and feedback pathways to maintain cell homeostasis, being thus important players in many physiological and pathological conditions. However, the functional classification of Ub-ligases needs to be revised and extended. Methods In the current study, we used a novel semantic biclustering technique for expression profiling of Ub-ligases and ubiquitination-related genes in the murine gastrointestinal tract (GIT). We accommodated a general framework of the algorithm for finding tissue-specific gene expression clusters in GIT. In order to test identified clusters in a biological system, we used a model of epithelial regeneration. For this purpose, a dextran sulfate sodium (DSS) mouse model, following with in situ hybridization, was used to expose genes with possible compensatory features. To determine cell-type specific distribution of Ub-ligases and ubiquitination-related genes, principal component analysis (PCA) and Uniform Manifold Approximation and Projection technique (UMAP) were used to analyze the Tabula Muris scRNA-seq data of murine colon followed by comparison with our clustering results. Results Our established clustering protocol, that incorporates the semantic biclustering algorithm, demonstrated the potential to reveal interesting expression patterns. In this manner, we statistically defined gene clusters consisting of the same genes involved in distinct regulatory pathways vs distinct genes playing roles in functionally similar signaling pathways. This allowed us to uncover the potentially redundant features of GIT-specific Ub-ligases and ubiquitination-related genes. Testing the statistically obtained results on the mouse model showed that genes clustered to the same ontology group simultaneously alter their expression pattern after induced epithelial damage, illustrating their complementary role during tissue regeneration. Conclusions An optimized semantic clustering protocol demonstrates the potential to reveal a readable and unique pattern in the expression profiling of GIT-specific Ub-ligases, exposing ontologically relevant gene clusters with potentially redundant features. This extends our knowledge of ontological relationships among Ub-ligases and ubiquitination-related genes, providing an alternative and more functional gene classification. In a similar way, semantic cluster analysis could be used for studding of other enzyme families, tissues and systems. |
| first_indexed | 2024-04-13T07:22:56Z |
| format | Article |
| id | doaj.art-e558a3d0012143f19359d963650b887f |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-04-13T07:22:56Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-e558a3d0012143f19359d963650b887f2022-12-22T02:56:33ZengBMCBMC Gastroenterology1471-230X2022-04-0122111410.1186/s12876-022-02265-2Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patternsVeronika Iatsiuk0Frantisek Malinka1Marketa Pickova2Jolana Tureckova3Jiri Klema4Frantisek Spoutil5Vendula Novosadova6Jan Prochazka7Radislav Sedlacek8Laboratory of Transgenic Models of Diseases and Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesLaboratory of Transgenic Models of Diseases and Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesLaboratory of Transgenic Models of Diseases and Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesLaboratory of Transgenic Models of Diseases and Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesDepartment of Computer Science, Czech Technical University in PragueLaboratory of Transgenic Models of Diseases and Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesLaboratory of Transgenic Models of Diseases and Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesLaboratory of Transgenic Models of Diseases and Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesLaboratory of Transgenic Models of Diseases and Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesAbstract Background Ubiquitin ligases (Ub-ligases) are essential intracellular enzymes responsible for the regulation of proteome homeostasis, signaling pathway crosstalk, cell differentiation and stress responses. Individual Ub-ligases exhibit their unique functions based on the nature of their substrates. They create a complex regulatory network with alternative and feedback pathways to maintain cell homeostasis, being thus important players in many physiological and pathological conditions. However, the functional classification of Ub-ligases needs to be revised and extended. Methods In the current study, we used a novel semantic biclustering technique for expression profiling of Ub-ligases and ubiquitination-related genes in the murine gastrointestinal tract (GIT). We accommodated a general framework of the algorithm for finding tissue-specific gene expression clusters in GIT. In order to test identified clusters in a biological system, we used a model of epithelial regeneration. For this purpose, a dextran sulfate sodium (DSS) mouse model, following with in situ hybridization, was used to expose genes with possible compensatory features. To determine cell-type specific distribution of Ub-ligases and ubiquitination-related genes, principal component analysis (PCA) and Uniform Manifold Approximation and Projection technique (UMAP) were used to analyze the Tabula Muris scRNA-seq data of murine colon followed by comparison with our clustering results. Results Our established clustering protocol, that incorporates the semantic biclustering algorithm, demonstrated the potential to reveal interesting expression patterns. In this manner, we statistically defined gene clusters consisting of the same genes involved in distinct regulatory pathways vs distinct genes playing roles in functionally similar signaling pathways. This allowed us to uncover the potentially redundant features of GIT-specific Ub-ligases and ubiquitination-related genes. Testing the statistically obtained results on the mouse model showed that genes clustered to the same ontology group simultaneously alter their expression pattern after induced epithelial damage, illustrating their complementary role during tissue regeneration. Conclusions An optimized semantic clustering protocol demonstrates the potential to reveal a readable and unique pattern in the expression profiling of GIT-specific Ub-ligases, exposing ontologically relevant gene clusters with potentially redundant features. This extends our knowledge of ontological relationships among Ub-ligases and ubiquitination-related genes, providing an alternative and more functional gene classification. In a similar way, semantic cluster analysis could be used for studding of other enzyme families, tissues and systems.https://doi.org/10.1186/s12876-022-02265-2Ub-ligaseGITRegenerationCluster analysisSemantic biclusteringGene redundancy |
| spellingShingle | Veronika Iatsiuk Frantisek Malinka Marketa Pickova Jolana Tureckova Jiri Klema Frantisek Spoutil Vendula Novosadova Jan Prochazka Radislav Sedlacek Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns BMC Gastroenterology Ub-ligase GIT Regeneration Cluster analysis Semantic biclustering Gene redundancy |
| title | Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns |
| title_full | Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns |
| title_fullStr | Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns |
| title_full_unstemmed | Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns |
| title_short | Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns |
| title_sort | semantic clustering analysis of e3 ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns |
| topic | Ub-ligase GIT Regeneration Cluster analysis Semantic biclustering Gene redundancy |
| url | https://doi.org/10.1186/s12876-022-02265-2 |
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