Integrating single-cell datasets produced by multiple omics technologies is essential for defining cellular heterogeneity. Mosaic integration, in which different datasets share only some of the measured modalities, poses major challenges, particularly regarding modality alignment and batch effect removal. Here, we present a deep probabilistic framework for the mosaic integration and knowledge transfer (MIDAS) of single-cell multimodal data. MIDAS simultaneously achieves dimensionality reduction, imputation and batch correction of mosaic data by using self-supervised modality alignment and information-theoretic latent disentanglement. We demonstrate its superiority to 19 other methods and reliability by evaluating its performance in trimodal and mosaic integration tasks. We also constructed a single-cell trimodal atlas of human peripheral blood mononuclear cells and tailored transfer learning and reciprocal reference mapping schemes to enable flexible and accurate knowledge transfer from the atlas to new data. Applications in mosaic integration, pseudotime analysis and cross-tissue knowledge transfer on bone marrow mosaic datasets demonstrate the versatility and superiority of MIDAS. MIDAS is available at https://github.com/labomics/midas.

Differential network analysis is an important tool to investigate the rewiring of gene interactions under different conditions. Several computational methods have been developed to estimate differential networks from gene expression data, but most of them do not consider that gene network rewiring may be driven by the differential expression of individual genes. New differential network analysis methods that simultaneously take account of the changes in gene interactions and changes in expression levels are needed. : In this article, we propose a differential network analysis method that considers the differential expression of individual genes when identifying differential edges. First, two hypothesis test statistics are used to quantify changes in partial correlations between gene pairs and changes in expression levels for individual genes. Then, an optimization framework is proposed to combine the two test statistics so that the resulting differential network has a hierarchical property, where a differential edge can be considered only if at least one of the two involved genes is differentially expressed. Simulation results indicate that our method outperforms current state-of-the-art methods. We apply our method to identify the differential networks between the luminal A and basal-like subtypes of breast cancer and those between acute myeloid leukemia and normal samples. Hub nodes in the differential networks estimated by our method, including both differentially and nondifferentially expressed genes, have important biological functions. All the datasets underlying this article are publicly available. Processed data and source code can be accessed through the Github repository at https://github.com/Zhangxf-ccnu/chNet. Supplementary data are available at Bioinformatics online.

This paper proposes a new multiobjective evolutionary algorithm based on the black hole algorithm with a new individual density assessment (cell density), called “adaptive multiobjective black hole algorithm” (AMOBH). Cell density has the characteristics of low computational complexity and maintains a good balance of convergence and diversity of the Pareto front. The framework of AMOBH can be divided into three steps. Firstly, the Pareto front is mapped to a new objective space called parallel cell coordinate system. Then, to adjust the evolutionary strategies adaptively, Shannon entropy is employed to estimate the evolution status. At last, the cell density is combined with a dominance strength assessment called cell dominance to evaluate the fitness of solutions. Compared with the state-of-the-art methods SPEA-II, PESA-II, NSGA-II, and MOEA/D, experimental results show that AMOBH has a good performance in terms of convergence rate, population diversity, population convergence, subpopulation obtention of different Pareto regions, and time complexity to the latter in most cases.

In Caenorhabditis elegans, a large number of protein–protein interactions (PPIs) are identified by different experiments. However, a comprehensive weighted PPI network, which is essential for signaling pathway inference, is not yet available in this model organism. Therefore, we firstly construct an integrative PPI network in C. elegans with 12 951 interactions involving 5039 proteins from seven molecular interaction databases. Then, a reliability score based on a probabilistic graphical model (RSPGM) is proposed to assess PPIs. It assumes that the random number of interactions between two proteins comes from the Bernoulli distribution to avoid multi-links. The main parameter of the RSPGM score contains a few latent variables which can be considered as several common properties between two proteins. Validations on high-confidence yeast datasets show that RSPGM provides more accurate evaluation than other approaches, and the PPIs in the reconstructed PPI network have higher biological relevance than that in the original network in terms of gene ontology, gene expression, essentiality and the prediction of known protein complexes. Furthermore, this weighted integrative PPI network in C. elegans is employed on inferring interaction path of the canonical Wnt/β-catenin pathway as well. Most genes on the inferred interaction path have been validated to be Wnt pathway components. Therefore, RSPGM is essential and effective for evaluating PPIs and inferring interaction path. Finally, the PPI network with RSPGM scores can be queried and visualized on a user interactive website, which is freely available at http://rspgm.bionetworks.tk/.

In this paper, a novel algorithm called a Nonlocal Adaptive Mean Filter (NAMF) for removing salt-and-pepper (SAP) noise from corrupted images is presented. We employ an efficient window detector with adaptive size to detect the noise. The noisy pixel is then replaced by the combination of its neighboring pixels, and finally, a SAP noise based nonlocal mean filter is used to reconstruct the intensity values of noisy pixels. Extensive experimental results demonstrate that NAMF can obtain better performance in terms of quality for restoring images at all levels of SAP noise.

Motivation: Cell fate specification plays a key role to generate distinct cell types during metazoan development. However, most of the underlying signaling networks at cellular level are not well understood. Availability of time lapse single-cell gene expression data collected throughout C. elegans embryogenesis provides an excellent opportunity for investigating signaling networks underlying cell fate specification at systems, cellular and molecular levels.