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Nature Papers Describe Cell Clustering Approach, Synthetic Genomics, More

A Wellcome Sanger Institute team has developed a new method to cluster cells by genotype using the genetic variants detected within the single-cell RNA sequencing reads. As reported in Nature Methods this week, the technique — called souporcell — uses sparse mixture model clustering with explicit ambient RNA modeling. In benchmarking experiments, souporcell outperforms existing methods, its developers write, and is robust across a range of parameters. "Moreover, souporcell is highly accurate for challenging datasets involving closely related maternal/fetal samples and varying mixtures of P. falciparum strains," they add.

The rapid genetic reconstruction of SARS-CoV-2 and other RNA viruses using a yeast-based synthetic genomics platform is described by a University of Bern-led team in Nature this week. While Escherichia coli is widely used to clone viral genomes, this host cannot easily handle the large genomes of coronaviruses. To overcome this, the scientists turned to Saccharomyces cerevisiae, which they use to clone, assemble and mutagenize full Mycoplasma genomes. With the platform, the researchers were able to engineer and resurrect chemically synthesized clones of SARS-CoV-2 within a week of receiving synthetic virus DNA fragments. "As the SARS-CoV-2 pandemic is ongoing, we expect to see sequence variations and possibly phenotypic changes of evolving SARS-CoV-2 in the human host," they write. Using their platform, "it is now possible to rapidly introduce such sequence variations into the infectious clone and to functionally characterize SARS-CoV-2 evolution in real-time." GenomeWeb has more on this, here.

Scientists from the Chinese Academy of Medical Sciences report in Nature Cell Biology this week on the use of single-cell RNA sequencing to observe how hematopoietic stem cells (HSCs) behave shortly after transplantation. The team used scRNA-seq to obtain transcriptome-based classifications of 28 hematopoietic cell types, which they then used in combination with functional assays to track the dynamic changes of immunophenotypically purified HSCs in irradiated recipients within the first week after transplantation. "In conjunction with classical function-based or immunophenotype-based definition, the current transcriptome-based classification of HSC or other regenerative cell populations at single-cell resolution by scRNA-seq offers a comprehensive yet powerful approach to dissect and track how stem cells better fit and replenish a damaged or diseased tissue, which also has important implications for further explorations and improvements of stem cell therapies," the study's authors write.