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SOJNMF: Identifying Multidimensional Molecular Regulatory Modules by Sparse Orthogonality-Regularized Joint
Abstract:
Cancer is not only a very aggressive but also a very diverse disease. Recent advances in high-throughput omics technologies of cancer have enabled biomedical researchers to have more opportunities for studying its multi-level biological regulatory mechanism. However, there are few methods to explore the underlying mechanism of cancer by identifying its multidimensional molecular regulatory modules from the multidimensional omics data of cancer. In this paper, we propose a sparse orthogonality-regularized joint non-negative matrix factorization (SOJNMF) algorithm which can integratively analyze multidimensional omics data. This method can not only identify multidimensional molecular regulatory modules, but reduce the overlap rate of features among the multidimensional modules while ensuring the sparsity of the coefficient matrix after decomposition. Gene expression data, miRNA expression data and gene methylation data of liver cancer are integratively analyzed based on SOJNMF algorithm. Then, we obtain 238 multidimensional molecular regulatory modules. The results of permutation test indicate that different omics features within these modules are significantly correlated in statistics. Meanwhile, the results of functional enrichment analysis show that these multidimensional modules are significantly related to the underlying mechanism of the occurrence and development of liver cancer.
Insights
This study introduces a new algorithm to analyze complex cancer data, identifying key molecular modules. This approach helps understand liver cancer mechanisms by integrating multiple data types.
Area of Science:
- Genomics
- Bioinformatics
- Cancer Research
Background:
- Cancer is a complex and diverse disease.
- High-throughput omics technologies offer new avenues for studying cancer's regulatory mechanisms.
- Existing methods are limited in exploring cancer mechanisms through multidimensional omics data.
Purpose of the Study:
- To propose a novel algorithm for integrative analysis of multidimensional omics data.
- To identify multidimensional molecular regulatory modules in cancer.
- To reduce feature overlap and ensure sparsity in module identification.
Main Methods:
- Developed a sparse orthogonality-regularized joint non-negative matrix factorization (SOJNMF) algorithm.
- Applied SOJNMF to integrate gene expression, miRNA expression, and gene methylation data from liver cancer.
- Utilized permutation tests and functional enrichment analysis.
Main Results:
- Identified 238 multidimensional molecular regulatory modules in liver cancer.
- Demonstrated statistically significant correlations between omics features within identified modules.
- Confirmed the association of these modules with liver cancer's occurrence and development mechanisms.
Conclusions:
- The SOJNMF algorithm effectively integrates multidimensional omics data for cancer research.
- The identified modules provide insights into the complex regulatory networks underlying liver cancer.
- This approach advances the understanding of cancer's multi-level biological mechanisms.
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