Motivation The rapid development of single-cell RNA sequencing (scRNA-seq) technologies allows us to explore tissue heterogeneity at the cellular level. The identification of cell types plays an essential role in the analysis of scRNA-seq data, which, in turn, influences the discovery of regulatory genes that induce heterogeneity. As the scale of sequencing data increases, the classical method of combining clustering and differential expression analysis to annotate cells becomes more costly in terms of both labor and resources. Existing scRNA-seq supervised classification method can alleviate this issue through learning a classifier trained on the labeled reference data and then making a prediction based on the unlabeled target data. However, such label transference strategy carries with risks, such as susceptibility to batch effect and further compromise of inherent discrimination of target data. Results In this paper, inspired by unsupervised domain adaptation, we propose a flexible single cell semi-supervised clustering and annotation framework, scSemiCluster, which integrates the reference data and target data for training. We utilize structure similarity regularization on the reference domain to restrict the clustering solutions of the target domain. We also incorporates pairwise constraints in the feature learning process such that cells belonging to the same cluster are close to each other, and cells belonging to different clusters are far from each other in the latent space. Notably, without explicit domain alignment and batch effect correction, scSemiCluster outperforms other state-of-the-art, single-cell supervised classification and semi-supervised clustering annotation algorithms in both simulation and real data. To the best of our knowledge, we are the first to use both deep discriminative clustering and deep generative clustering techniques in the single-cell field. Availability An implementation of scSemiCluster is available from https://github.com/xuebaliang/scSemiCluster. Supplementary information Supplementary notes are available at Bioinformatics online.

As single-cell RNA sequencing technologies mature, massive gene expression profiles can be obtained. Consequently, cell clustering and annotation become two crucial and fundamental procedures affecting other specific downstream analyses. Most existing single-cell RNA-seq (scRNA-seq) data clustering algorithms do not take into account the available cell annotation results on the same tissues or organisms from other laboratories. Nonetheless, such data could assist and guide the clustering process on the target dataset. Identifying marker genes through differential expression analysis to manually annotate large amounts of cells also costs labor and resources. Therefore, in this paper, we propose a novel end-to-end cell supervised clustering and annotation framework called scAnCluster, which fully utilizes the cell type labels available from reference data to facilitate the cell clustering and annotation on the unlabeled target data. Our algorithm integrates deep supervised learning, self-supervised learning and unsupervised learning techniques together, and it outperforms other customized scRNA-seq supervised clustering methods in both simulation and real data. It is particularly worth noting that our method performs well on the challenging task of discovering novel cell types that are absent in the reference data.

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Microbes can survive in some extreme environments and can be found almost everywhere in the world. Microbial communities have been found to be associated with higher live forms, including animals and plants. Microbes can affect processes from food production to human health, such as disease and homeostasis. Such microbes are not isolated, but rather interact with each other and establish connections with their living environments. Understanding these interactions is essential to an understanding of the organization and complex interplay of microbial communities, as well as the structure and dynamics of various ecosystems. A common and essential approach toward this objective involves the inference of microbiome interaction networks. Although network inference methods in other fields have been studied before, applying these methods to estimate microbiome associations based on compositional data will not yield valid results. On the one hand, features of microbiome data such as compositionality, sparsity and high-dimensionality challenge the data normalization and the design of computational methods. On the other hand, several issues like microbial community heterogeneity, external environmental interference and biological concerns also make it more difficult to deal with the network inference. In this paper, we provide a comprehensive review of emerging microbiome interaction network inference methods. According to various assumptions and research targets, estimated networks are divided into four main categories: correlation networks, conditional correlation networks, mixture networks and differential networks. Their scope of applications, advantages, as well as limitations, are presented in this review. Since real microbial interactions can be complex and dynamic, no unifying method has, to date, captured all the aspects of interest. In addition, we discuss the challenges now confronting current microbial associations study and future prospects. Finally, we highlight that the research in microbial network inference requires the joint promotion of statistical computation methods and experimental techniques. Codes of most methods introduced in this review will be collected in https://github.com/Qiuyanhe/Statisticalcomputation-methods-for-microbiome-compositional-data-network-inference.