scMCs: a framework for single-cell multi-omics data integration and multiple clusterings.

MOTIVATION: The integration of single-cell multi-omics data can uncover the underlying regulatory basis of diverse cell types and states. However, contemporary methods disregard the omics individuality, and the high noise, sparsity, and heterogeneity of single-cell data also impact the fusion effect. Furthermore, available single-cell clustering methods only focus on the cell type clustering, which cannot mine the alternative clustering to comprehensively analyze cells. RESULTS: We propose a single-cell data fusion based multiple clustering (scMCs) approach that can jointly model single-cell transcriptomics and epigenetic data, and explore multiple different clusterings. scMCs first mines the omics-specific and cross-omics consistent representations, then fuses them into a co-embedding representation, which can dissect cellular heterogeneity and impute data. To discover the potential alternative clustering embedded in multi-omics, scMCs projects the co-embedding representation into different salient subspaces. Meanwhile, it reduces the redundancy between subspaces to enhance the diversity of alternative clusterings and optimizes the cluster centers in each subspace to boost the quality of corresponding clustering. Unlike single clustering, these alternative clusterings provide additional perspectives for understanding complex genetic information, such as cell types and states. Experimental results show that scMCs can effectively identify subcellular types, impute dropout events, and uncover diverse cell characteristics by giving different but meaningful clusterings. AVAILABILITY AND IMPLEMENTATION: The code is available at www.sdu-idea.cn/codes.php?name=scMCs.

Correntropy induced loss based sparse robust graph regularized extreme learning machine for cancer classification.

BACKGROUND: As a machine learning method with high performance and excellent generalization ability, extreme learning machine (ELM) is gaining popularity in various studies. Various ELM-based methods for different fields have been proposed. However, the robustness to noise and outliers is always the main problem affecting the performance of ELM. RESULTS: In this paper, an integrated method named correntropy induced loss based sparse robust graph regularized extreme learning machine (CSRGELM) is proposed. The introduction of correntropy induced loss improves the robustness of ELM and weakens the negative effects of noise and outliers. By using the L2,1-norm to constrain the output weight matrix, we tend to obtain a sparse output weight matrix to construct a simpler single hidden layer feedforward neural network model. By introducing the graph regularization to preserve the local structural information of the data, the classification performance of the new method is further improved. Besides, we design an iterative optimization method based on the idea of half quadratic optimization to solve the non-convex problem of CSRGELM. CONCLUSIONS: The classification results on the benchmark dataset show that CSRGELM can obtain better classification results compared with other methods. More importantly, we also apply the new method to the classification problems of cancer samples and get a good classification effect.

Single-cell RNA-seq data clustering by deep information fusion.

Determining cell types by single-cell transcriptomics data is fundamental for downstream analysis. However, cell clustering and data imputation still face the computation challenges, due to the high dropout rate, sparsity and dimensionality of single-cell data. Although some deep learning based solutions have been proposed to handle these challenges, they still can not leverage gene attribute information and cell topology in a sensible way to explore the consistent clustering. In this paper, we present scDeepFC, a deep information fusion-based single-cell data clustering method for cell clustering and data imputation. Specifically, scDeepFC uses a deep auto-encoder (DAE) network and a deep graph convolution network to embed high-dimensional gene attribute information and high-order cell-cell topological information into different low-dimensional representations, and then fuses them to generate a more comprehensive and accurate consensus representation via a deep information fusion network. In addition, scDeepFC integrates the zero-inflated negative binomial (ZINB) into DAE to model the dropout events. By jointly optimizing the ZINB loss and cell graph reconstruction loss, scDeepFC generates a salient embedding representation for clustering cells and imputing missing data. Extensive experiments on real single-cell datasets prove that scDeepFC outperforms other popular single-cell analysis methods. Both the gene attribute and cell topology information can improve the cell clustering.

L2,1-Extreme Learning Machine: An Efficient Robust Classifier for Tumor Classification.

With the development of cancer research, various gene expression datasets containing cancer information show an explosive growth trend. In addition, due to the continuous maturity of single-cell RNA sequencing (scRNA-seq) technology, the protein information and pedigree information of a single cell are also continuously mined. It is a technical problem of how to classify these high-dimensional data correctly. In recent years, Extreme Learning Machine (ELM) has been widely used in the field of supervised learning and unsupervised learning. However, the traditional ELM does not consider the robustness of the method. To improve the robustness of ELM, in this paper, a novel ELM method based on L2,1-norm named L2,1-Extreme Learning Machine (L2,1 -ELM) has been proposed. The method introduces L2,1-norm on loss function to improve the robustness, and minimizes the influence of noise and outliers. Firstly, we evaluate the new method on five UCI datasets. The experiment results prove that our method can achieve competitive results. Next, the novel method is applied to the problem of classification of cancer samples and single-cell RNA sequencing datasets. The experimental results on The Cancer Genome Atlas (TCGA) datasets and scRNA-seq datasets prove that ELM and its variants has great potential in the classification of cancer samples.