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EC-PGMGR: Ensemble Clustering Based on Probability Graphical Model With Graph Regularization for Single-Cell RNA-seq Data.

ABSTRACT: Advances in technology have made it convenient to obtain a large amount of single cell RNA sequencing (scRNA-seq) data. Since that clustering is a very important step in identifying or defining cellular phenotypes, many clustering approaches have been developed recently for these applications. The general methods can be roughly divided into normal clustering methods and integrated (ensemble) clustering methods which combine more than two normal clustering methods aiming to get much more informative performance. In order to make a contrast with the integrated clustering algorithm, the normal clustering method is often called individual or base clustering method. Note that the results of many individual clustering methods are often developed to capture one aspect of the data, and the results depend on the initial parameter settings, such as cluster number, distance metric and so on. Compared with individual clustering, although integrative clustering method may get much more accurate performance, the results depend on the base clustering results and integrated systems are often not self-regulation. Therefore, how to design a robust unsupervised clustering method is still a challenge. In order to tackle above limitations, we propose a novel Ensemble Clustering algorithm based on Probability Graphical Model with Graph Regularization, which is called EC-PGMGR for short. On one hand, we use parameter controlling in Probability Graphical Model (PGM) to automatically determine the cluster number without prior knowledge. On the other hand, we add a regularization term to reduce the effect deriving from some weak base clustering results. Particularly, the integrative results collected from base clustering methods can be assembled in the form of combination with self-regulation weights through a pre-learning process, which can efficiently enhance the effect of active clustering methods while weaken the effect of inactive clustering methods. Experiments are carried out on 7 data sets generated by different platforms with the number of single cells from 822 to 5,132. Results show that EC-PGMGR performs better than 4 alternative individual clustering methods and 2 ensemble methods in terms of accuracy including Adjusted Rand Index (ARI) and Normalized Mutual Information (NMI), robustness, effectiveness and so on. EC-PGMGR provides an effective way to integrate different clustering results for more accurate and reliable results in further biological analysis as well. It may provide some new insights to the other applications of clustering.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC7673820 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:MotivationSingle-cell RNA sequencing (scRNA-seq) is an increasingly popular technique for transcriptomic analysis of gene expression at the single-cell level. Cell-type clustering is the first crucial task in the analysis of scRNA-seq data that facilitates accurate identification of cell types and the study of the characteristics of their transcripts. Recently, several computational models based on a deep autoencoder and the ensemble clustering have been developed to analyze scRNA-seq data. However, current deep autoencoders are not sufficient to learn the latent representations of scRNA-seq data, and obtaining consensus partitions from these feature representations remains under-explored.ResultsTo address this challenge, we propose a single-cell deep clustering model via a dual denoising autoencoder with bipartite graph ensemble clustering called scBGEDA, to identify specific cell populations in single-cell transcriptome profiles. First, a single-cell dual denoising autoencoder network is proposed to project the data into a compressed low-dimensional space and that can learn feature representation via explicit modeling of synergistic optimization of the zero-inflated negative binomial reconstruction loss and denoising reconstruction loss. Then, a bipartite graph ensemble clustering algorithm is designed to exploit the relationships between cells and the learned latent embedded space by means of a graph-based consensus function. Multiple comparison experiments were conducted on 20 scRNA-seq datasets from different sequencing platforms using a variety of clustering metrics. The experimental results indicated that scBGEDA outperforms other state-of-the-art methods on these datasets, and also demonstrated its scalability to large-scale scRNA-seq datasets. Moreover, scBGEDA was able to identify cell-type specific marker genes and provide functional genomic analysis by quantifying the influence of genes on cell clusters, bringing new insights into identifying cell types and characterizing the scRNA-seq data from different perspectives.Availability and implementationThe source code of scBGEDA is available at https://github.com/wangyh082/scBGEDA. The software and the supporting data can be downloaded from https://figshare.com/articles/software/scBGEDA/19657911.Supplementary informationSupplementary data are available at Bioinformatics online.

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EC-PGMGR: Ensemble Clustering Based on Probability Graphical Model With Graph Regularization for Single-Cell RNA-seq Data.

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