Abstract Motivation Inferring gene networks from single-cell RNA sequencing data is challenging due to high sparsity, dimensionality, and technical noise. Current pipelines lack the multi-dataset integration and comprehensive post-processing analysis. Results scGraphVerse is an R package that integrates multiple algorithms (GENIE3, GRNBoost2, ZILGM, PCzinb, and JRF) with extensive evaluation and visualization tools. Its modular workflow supports early, late, and joint integration strategies for multi-dataset analysis, providing standardized input/output interfaces and biological interpretation tools, including community detection, pathway enrichment, and literature mining. Benchmarking on simulated data showed model-based methods (PCzinb and ZILGM) perform well with limited sample sizes, while JRF performs best as the network size and dataset numbers increase. A PBMC case study demonstrates JRF’s ability to identify literature-supported regulatory communities across donors. Availability and implementation The package is available in Bioconductor 3.22 at https://bioconductor.org/packages/release/bioc/html/scGraphVerse.html. Code and examples: https://github.com/ngsFC/scGV_analysis.
Francesco Cecere, D. De Canditiis, Annamaria Carissimo et al.· Bioinformatics Advances· 0 citations
Conventional annotation of single-cell RNA-sequencing (scRNA-seq) data relies heavily on manual, marker-based thresholding, an approach that can obscure subtle transcriptomic gradients and collapse functionally distinct cell states into broad, heterogeneous populations. Here we apply the Gaussian multi-Graphical Model (GmGM) framework, which jointly infers cell-cell and gene-gene dependency structure from a single scRNA-seq data matrix, to a 10x Genomics PBMC dataset. Ten independent GMGM-Leiden clustering runs were integrated into a robust consensus partition using a soft cluster ensemble approach and benchmarked against reference cell-type annotations. This strategy yielded stable cluster partitions that resolve biologically meaningful sub-populations not distinguished by the reference annotation. In parallel, for each cluster, gene co-expression modules were extracted from the fitted model via consensus Leiden clustering across resolutions, evaluated using standard network metrics, and validated functionally with the Network Enrichment Analysis Test (NEAT), which confirmed non-random enrichment signal. A module-scoring procedure linked network topology to per-cell, per-cluster expression signatures, and a novel extension of GmGM, recovering a shared cell-cell network together with population-specific gene networks in a single model run, was demonstrated in a case study on the CD4+ T-cell population. These results indicate that GmGM provides a unified, reproducible framework for joint cell clustering and gene-network inference, capable of revealing cellular structure beyond that captured by conventional pipelines.
O. Lanzetta, L. Cutillo, Bailey Andrew et al.· 0 citations
