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Abstract Inferring gene regulatory networks from single-cell RNA-sequencing trajectories has been an active area of research yet methods are still needed to identify regulators governing cell transitions. We developed DREAMIT (Dynamic Regulation of Expression Across Modules in Inferred Trajectories) to annotate transcription-factor activity along single-cell trajectory branches, using ensembles of relations to target genes. Using a benchmark representing several different tissues, as well as external validation with ATAC-Seq and Perturb-Seq data on hematopoietic cells, the method was found to have higher tissue-specific sensitivity and specificity over competing approaches.

Abstract The SARS-CoV-2 pandemic has challenged humankind’s ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, identifying therapeutic interventions and drug targets for patients infected with the virus remains important as new strains of the virus evolve, or future coronaviruses may emerge that are resistant to current vaccines. The application of transcriptomic RNA sequencing of infected samples may shed new light on the pathways involved in viral mechanisms and host responses. We describe the application of the previously developed “dual RNA-seq” approach to investigate, for the first time, the co-regulation between the human and SARS-CoV-2 transcriptomes. Together with differential expression analysis, we describe the tissue specificity of SARS-CoV-2 expression, an inferred lipopolysaccharide response, and co-regulation of CXCL’s, SPRR’s, S100’s with SARS-CoV-2 expression. Lipopolysaccharide response pathways in particular offer promise for future therapeutic research and the prospect of subgrouping patients based on chemokine expression that may help explain the vastly different reactions patients have to infection. Taken together these findings highlight unappreciated SARS-CoV-2 expression signatures and emphasize new considerations and mechanisms for SARS-CoV-2 therapeutic intervention.