Mining functional gene modules by multi-view NMF of phenome-genome association
Abstract Background Mining functional gene modules from genomic data is an important step to detect gene members of pathways or other relations such as protein-protein interactions. This work explores the plausibility of detecting functional gene modules by factorizing gene-phenotype association mat...
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BMC
2025-01-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-024-11120-5 |
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| author | Xu Jin WenQian He MingMing Liu Lin Wang YaoGong Zhang YingJie Xu Ling Ma YaLou Huang MaoQiang Xie |
| author_facet | Xu Jin WenQian He MingMing Liu Lin Wang YaoGong Zhang YingJie Xu Ling Ma YaLou Huang MaoQiang Xie |
| author_sort | Xu Jin |
| collection | DOAJ |
| description | Abstract Background Mining functional gene modules from genomic data is an important step to detect gene members of pathways or other relations such as protein-protein interactions. This work explores the plausibility of detecting functional gene modules by factorizing gene-phenotype association matrix from the phenotype ontology data rather than the conventionally used gene expression data. Recently, the hierarchical structure of phenotype ontologies has not been sufficiently utilized in gene clustering while functionally related genes are consistently associated with phenotypes on the same path in phenotype ontologies. Results This work demonstrates a hierarchical Nonnegative Matrix Factorization (NMF) framework, called Consistent Multi-view Nonnegative Matrix Factorization (CMNMF), which factorizes genome-phenome association matrix at consecutive levels of the hierarchical structure in phenotype ontology to mine functional gene modules. CMNMF constrains the gene clusters from the association matrices at two consecutive levels to be consistent since the genes are annotated with both the child-level phenotypes and the parent-level phenotypes in two levels. CMNMF also restricts the identified gene clusters to be densely connected in the phenotype ontology hierarchy. In the experiments on mining functionally related genes from mouse phenotype ontology and human phenotype ontology, CMNMF effectively improves clustering performance over the baseline methods. Gene ontology enrichment analysis is also conducted to verify its practical effectiveness to reveal meaningful gene modules. Conclusions Utilizing the information in the hierarchical structure of phenotype ontology, CMNMF can identify functional gene modules with more biological significance than conventional methods. CMNMF can also be a better tool for predicting members of gene pathways and protein-protein interactions. |
| format | Article |
| id | doaj-art-1deff2d0ebda4c14981e737cea73ab5f |
| institution | Kabale University |
| issn | 1471-2164 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj-art-1deff2d0ebda4c14981e737cea73ab5f2025-01-12T12:09:09ZengBMCBMC Genomics1471-21642025-01-0123S611510.1186/s12864-024-11120-5Mining functional gene modules by multi-view NMF of phenome-genome associationXu Jin0WenQian He1MingMing Liu2Lin Wang3YaoGong Zhang4YingJie Xu5Ling Ma6YaLou Huang7MaoQiang Xie8College of Software, Nankai UniversityCollege of Software, Nankai UniversityCollege of Software, Nankai UniversityCollege of Software, Nankai UniversityCollege of Software, Nankai UniversityCollege of Software, Nankai UniversityCollege of Software, Nankai UniversityTianJin International Joint Academy of BiomedicineCollege of Software, Nankai UniversityAbstract Background Mining functional gene modules from genomic data is an important step to detect gene members of pathways or other relations such as protein-protein interactions. This work explores the plausibility of detecting functional gene modules by factorizing gene-phenotype association matrix from the phenotype ontology data rather than the conventionally used gene expression data. Recently, the hierarchical structure of phenotype ontologies has not been sufficiently utilized in gene clustering while functionally related genes are consistently associated with phenotypes on the same path in phenotype ontologies. Results This work demonstrates a hierarchical Nonnegative Matrix Factorization (NMF) framework, called Consistent Multi-view Nonnegative Matrix Factorization (CMNMF), which factorizes genome-phenome association matrix at consecutive levels of the hierarchical structure in phenotype ontology to mine functional gene modules. CMNMF constrains the gene clusters from the association matrices at two consecutive levels to be consistent since the genes are annotated with both the child-level phenotypes and the parent-level phenotypes in two levels. CMNMF also restricts the identified gene clusters to be densely connected in the phenotype ontology hierarchy. In the experiments on mining functionally related genes from mouse phenotype ontology and human phenotype ontology, CMNMF effectively improves clustering performance over the baseline methods. Gene ontology enrichment analysis is also conducted to verify its practical effectiveness to reveal meaningful gene modules. Conclusions Utilizing the information in the hierarchical structure of phenotype ontology, CMNMF can identify functional gene modules with more biological significance than conventional methods. CMNMF can also be a better tool for predicting members of gene pathways and protein-protein interactions.https://doi.org/10.1186/s12864-024-11120-5Nonnegative matrix factorizationGene module miningPhenotype ontologyHierarchical structure |
| spellingShingle | Xu Jin WenQian He MingMing Liu Lin Wang YaoGong Zhang YingJie Xu Ling Ma YaLou Huang MaoQiang Xie Mining functional gene modules by multi-view NMF of phenome-genome association BMC Genomics Nonnegative matrix factorization Gene module mining Phenotype ontology Hierarchical structure |
| title | Mining functional gene modules by multi-view NMF of phenome-genome association |
| title_full | Mining functional gene modules by multi-view NMF of phenome-genome association |
| title_fullStr | Mining functional gene modules by multi-view NMF of phenome-genome association |
| title_full_unstemmed | Mining functional gene modules by multi-view NMF of phenome-genome association |
| title_short | Mining functional gene modules by multi-view NMF of phenome-genome association |
| title_sort | mining functional gene modules by multi view nmf of phenome genome association |
| topic | Nonnegative matrix factorization Gene module mining Phenotype ontology Hierarchical structure |
| url | https://doi.org/10.1186/s12864-024-11120-5 |
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