SUMMARY: Several methods have been developed in the past years to infer cell-cell communication networks from transcriptomic data based on ligand and receptor expression. Among them, ICELLNET is one of the few approaches to consider the multiple subunits of ligands and receptors complexes to infer and quantify cell communication. In here, we present a major update of ICELLNET. As compared to its original implementation, we (i) drastically expanded the ICELLNET ligand-receptor database from 380 to 1669 biologically curated interactions, (ii) integrated important families of communication molecules involved in immune crosstalk, cell adhesion, and Wnt pathway, (iii) optimized ICELLNET framework for single-cell RNA sequencing data analyses, (iv) provided new visualizations of cell-cell communication results to facilitate prioritization and biological interpretation. This update will broaden the use of ICELLNET by the scientific community in different biological fields. AVAILABILITY AND IMPLEMENTATION: ICELLNET package is implemented in R. Source code, documentation and tutorials are available on GitHub (https://github.com/soumelis-lab/ICELLNET).

MOTIVATION: Single-cell RNA-seq (scRNAseq) datasets are characterized by large ambient dimensionality, and their analyses can be affected by various manifestations of the dimensionality curse. One of these manifestations is the hubness phenomenon, i.e. existence of data points with surprisingly large incoming connectivity degree in the datapoint neighbourhood graph. Conventional approach to dampen the unwanted effects of high dimension consists in applying drastic dimensionality reduction. It remains unexplored if this step can be avoided thus retaining more information than contained in the low-dimensional projections, by correcting directly hubness. RESULTS: We investigated hubness in scRNAseq data. We show that hub cells do not represent any visible technical or biological bias. The effect of various hubness reduction methods is investigated with respect to the clustering, trajectory inference and visualization tasks in scRNAseq datasets. We show that hubness reduction generates neighbourhood graphs with properties more suitable for applying machine learning methods; and that it outperforms other state-of-the-art methods for improving neighbourhood graphs. As a consequence, clustering, trajectory inference and visualization perform better, especially for datasets characterized by large intrinsic dimensionality. Hubness is an important phenomenon characterizing data point neighbourhood graphs computed for various types of sequencing datasets. Reducing hubness can be beneficial for the analysis of scRNAseq data with large intrinsic dimensionality in which case it can be an alternative to drastic dimensionality reduction. AVAILABILITY AND IMPLEMENTATION: The code used to analyze the datasets and produce the figures of this article is available from https://github.com/sysbio-curie/schubness. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.