MBMM: Moment Estimating Beta Mixture Model-Based Clustering Algorithm for m6A Co-methylation Module Mining

2021 ◽  
Vol 16 ◽  
Author(s):  
Zhaoyang Liu ◽  
Hongsheng Yin ◽  
Shutao Chen ◽  
Hui Liu ◽  
Jia Meng ◽  
...  

Background: m6A methylation is a ubiquitous post-transcriptional modification that exists in mammals. MeRIP-seq technology makes the acquisition of m6A data in the whole transcriptome under different conditions realizable. The specific regulation of the enzyme will present co-methylation module on m6A methylation level data. Thus, mining the co-methylation module from which can help to unveil the mechanism of m<sup>6</sup>A methylation modification and its mechanism in the occurrence and development of complex diseases such as cancer. Objective: To develop a clustering algorithm that can effectively realize the mining of m6 co-methylation module. Method: In this study, a novel beta mixture model-based clustering algorithm named MBMM was proposed, which is based on the EM framework and introduces the method of moment estimating in M-step for parameter estimation to tackle the high-dimensional small sample m6A data. Simulation research was employed to evaluate the clustering performance of the proposed algorithm, and by which the co-methylation module mining was done based on real data. Biological significance correlation analysis was employed to explore whether the clustering results are co-methylation modules. Results and Conclusion: Simulation research demonstrated that MBMM performed out than other clustering algorithms. In real data, seven co-methylation modules were found by MBMM. Six m6A-related pathways specific analysis showed that six co-methylation modules were enriched in the pathway and were different. Five enzymes substrate-specific analysis revealed that seven co-methylation modules expressed varying degrees of enrichment. Gene Ontology enrichment analysis indicated that these modules may be regulated by enzymes while having potential functional specificity.

2022 ◽  
Vol 32 (1) ◽  
pp. 361-375
Author(s):  
S. Markkandan ◽  
S. Sivasubramanian ◽  
Jaison Mulerikkal ◽  
Nazeer Shaik ◽  
Beulah Jackson ◽  
...  

Author(s):  
Fadhaa Ali ◽  
Jian Zhang

AbstractMultilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated disease penetrances. A theoretical justification of the above model is provided. Furthermore, we introduce a hypothesis test for haplotype inheritance patterns which underpin this model. The performance of the proposed approach is evaluated by simulations and real data analysis. The results show that the proposed approach outperforms an existing multiple testing method.


2020 ◽  
Author(s):  
Takayuki Osabe ◽  
Kentaro Shimizu ◽  
Koji Kadota

Abstract Background RNA-seq is a tool for measuring gene expression and is commonly used to identify differentially expressed genes (DEGs). Gene clustering is used to classify DEGs with similar expression patterns for the subsequent analyses of data from experiments such as time-courses or multi-group comparisons. However, gene clustering has rarely been used for analyzing simple two-group data or differential expression (DE). In this study, we report a model-based clustering algorithm, MBCluster.Seq, that can be implemented using an R package for DE analysis.Results The input data originally used by MBCluster.Seq is DEGs, and the proposed method (called MBCdeg) uses all genes for the analysis. The method uses posterior probabilities of genes assigned to a cluster displaying non-DEG pattern for overall gene ranking. We compared the performance of MBCdeg with conventional R packages such as edgeR, DESeq2, and TCC that are specialized for DE analysis using simulated and real data. Our results showed that MBCdeg outperformed other methods when the proportion of DEG was less than 50%. However, the DEG identification using MBCdeg was less consistent than with conventional methods. We compared the effects of different normalization algorithms using MBCdeg, and performed an analysis using MBCdeg in combination with a robust normalization algorithm (called DEGES) that was not implemented in MBCluster.Seq. The new analysis method showed greater stability than using the original MBCdeg with the default normalization algorithm.Conclusions MBCdeg with DEGES normalization can be used in the identification of DEGs when the PDEG is relatively low. As the method is based on gene clustering, the DE result includes information on which expression pattern the gene belongs to. The new method may be useful for the analysis of time-course and multi-group data, where the classification of expression patterns is often required.


Author(s):  
Naohiko Kinoshita ◽  
◽  
Yasunori Endo ◽  
Akira Sugawara ◽  
◽  
...  

Clustering is representative unsupervised classification. Many researchers have proposed clustering algorithms based on mathematical models – methods we call model-based clustering. Clustering techniques are very useful for determining data structures, but model-based clustering is difficult to use for analyzing data correctly because we cannot select a suitable method unless we know the data structure at least partially. The new clustering algorithm we propose introduces soft computing techniques such as fuzzy reasoning in what we call linguistic-based clustering, whose features are not incident to the data structure. We verify the method’s effectiveness through numerical examples.


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