Summary: Sambamba is a high-performance robust tool and library for working with SAM, BAM and CRAM sequence alignment files; the most common file formats for aligned next generation sequencing data. Sambamba is a faster alternative to samtools that exploits multi-core processing and dramatically reduces processing time. Sambamba is being adopted at sequencing centers, not only because of its speed, but also because of additional functionality, including coverage analysis and powerful filtering capability. Availability and implementation: Sambamba is free and open source software, available under a GPLv2 license. Sambamba can be downloaded and installed from http://www.open-bio.org/wiki/Sambamba. Sambamba v0.5.0 was released with doi:10.5281/zenodo.13200. Contact: j.c.p.prins@umcutrecht.nl

Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy.

Intestinal organoids as an infection model: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an influenza-like disease with a respiratory transmission route; however, patients often present with gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Moreover, the virus has been detected in anal swabs, and cells in the inner-gut lining express the receptor that SARS-CoV-2 uses to gain entry to cells. Lamers et al. used human intestinal organoids, a “mini-gut” cultured in a dish, to demonstrate that SARS-CoV-2 readily replicates in an abundant cell type in the gut lining—the enterocyte—resulting in the production of large amounts of infective virus particles in the intestine. This work demonstrates that intestinal organoids can serve as a model to understand SARS-CoV-2 biology and infectivity in the gut. Science , this issue p. 50