Reconstruction of the cell pseudo-space from single-cell RNA sequencing data with scSpace.

Tissues are highly complicated with spatial heterogeneity in gene expression. However, the cutting-edge single-cell RNA-seq technology eliminates the spatial information of individual cells, which contributes to the characterization of cell identities. Herein, we propose single-cell spatial position associated co-embeddings (scSpace), an integrative method to identify spatially variable cell subpopulations by reconstructing cells onto a pseudo-space with spatial transcriptome references (Visium, STARmap, Slide-seq, etc.). We benchmark scSpace with both simulated and biological datasets, and demonstrate that scSpace can accurately and robustly identify spatially variated cell subpopulations. When employed to reconstruct the spatial architectures of complex tissue such as the brain cortex, the small intestinal villus, the liver lobule, the kidney, the embryonic heart, and others, scSpace shows promising performance on revealing the pairwise cellular spatial association within single-cell data. The application of scSpace in melanoma and COVID-19 exhibits a broad prospect in the discovery of spatial therapeutic markers.

Tracing the cell-type-specific modules of immune responses during COVID-19 progression using scDisProcema.

COVID-19 has caused severe threats to lives and damage to property worldwide. The immunopathology of the disease is of particular concern. Currently, researchers have used gene co-expression networks (GCNs) to deepen the study of molecular mechanisms of immune responses to COVID-19. However, most efforts have not fully explored dynamic changes of cell-type-specific molecular networks in the disease process. This study proposes a GCN construction pipeline named single-cell Disease Progression cellular module analysis (scDisProcema), which can trace dynamic changes of immune system response during disease progression using single-cell data. Here, scDisProcema considers changes in cell fate and expression patterns during disease development, identifying gene modules responsible for different immune cells. The hub genes are screened for each module by the specific expression level and the intercellular connectivity of modules. Based on functional items enriched by each gene module, we elucidate the biological processes of different cells involved in disease development and explain the molecular mechanisms underlying the process of cell depletion or proliferation caused by disease. Compared with traditional WGCNA methods, scDisProcema can make more convenient use of the heterogeneity information provided by scRNA-seq data and has great potential in exploring molecular changes during disease progression and organ development.

[Mechanism of Xuanfei Baidu Tang in treatment of COVID-19 based on network pharmacology].

The study aimed to investigate the multi-constituent, multi-target mechanism of Xuanfei Baidu Tang(XFBD) in the treatment of coronavirus disease 2019(COVID-19), through exploring the main ingredients and effective targets of XFBD, as well as analyzing the correlation between XFBD targets and COVID-19. The compounds of each herb in XFBD were collected from TCM-PTD, ETCM, TCMSP and SymMap database. Next, the information of meridian tropisms was collected from Chinese Pharmacopoeia(2015 edition), and the target information of the major constituents of XFBD were obtained from TCM-PTD, ETCM, TCMSP and TargetNet database. Subsequently, the target network model and the major modules were generated by Cytoscape, and the functional enrichment analysis of XFBD targets were completed by DAVID and STRING. As a result, ten of the 13 herbs in XFBD belonged to the lung meridian, and 326 of the 1 224 putative XFBD targets were associated with the disease target of COVID-19, among which 109 targets were enriched in the disease pathways of viral infection and lung injury. The main biological pathways regulated by the key XFBD targets included viral infection, energy metabolism, immunity and inflammation, parasites and bacterial infections. In conclusion, the therapeutic mechanism of XFBD in COVID-19 showed a multi-herb, multi-constituent, multi-target pattern, with lung as the chief targeted organ. By regulating a series of biological pathways closely related to the occurrence and development of diseases, XFBD plays a role in balancing immunity, eliminating inflammation, regulating hepatic and biliary metabolism and recovering energy metabolism balance.