A new computational method for automated genome assembly from long, high-fidelity reads is presented in Nature Biotechnology this week. While breakthroughs in genome sequencing were primarily achieved using HiFi reads, assembly of these reads remains a challenge and, in the era of population-scale sequencing, there is a need for an accurate tool for complete genome assembly. To that end, researchers from the University of California, San Diego, developed the La Jolla Assembler (LJA), a fast algorithm using the Bloom filter, sparse de Bruijn graphs, and disjointig generation. According to the researchers, LJA outperforms current state-of-the-art assemblers, achieving five-fold fewer misassemblies while generating more contiguous assemblies.
By sequencing the gut microbiomes of cancer patients undergoing treatment with immune checkpoint inhibitors (ICIs), a team led by investigators from King's College London and the University of Trento have uncovered a new details about the link between the gut microbiome and clinical responses to this class of cancer immunotherapeutics. Looking to extend previous research associating the composition of the gut microbiome to the effects of ICIs, the scientists performed shotgun metagenomic sequencing on 165 stool samples collected from patients with advanced cutaneous melanoma prior to receiving ICI treatment, then integrated the data with 147 metagenomic samples from previously published studies. As reported in Nature Medicine this week, they find a relevant, but cohort-dependent, association between the gut microbiome and ICI response. While they identified a panel of microbial species associated with those who responded to treatment, "no single species could be regarded as a fully consistent biomarker across studies," the researchers write. "Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders."
A single-cell multi-omics analysis of human pancreatic islets is presented in this week's Nature Metabolism, shedding new cellular and molecular insights into type 1 diabetes (T1D) pathogenesis. T1D is an autoimmune disease characterized by the destruction of insulin-producing beta cells in the islets of Langerhans within the pancreas by cytotoxic CD8+ T cells. Aiming to gain insights into the etiology of this complex disease, scientists from the University of Pennsylvania built a pancreatic islet atlas containing around 80,000 cells using single-cell transcriptomics, roughly 7,000,000 cells using cytometry by time of flight, and approximately 1,000,000 cells using imaging mass cytometry in pancreatic tissues of human organ donors both with and without T1D. Using an analytical strategy to assess pancreatic islets and identify canonical cell types, they show that a subset of exocrine ductal cells acquires a signature of tolerogenic dendritic cells in an apparent attempt at immune suppression in T1D donors.