We introduce volumetric DNA microscopy, a technique that enables three-dimensional imaging of tissue morphology and gene expression in a single measurement. This feat is achieved by forming a huge intermolecular network of DNA barcodes within an intact specimen and encoding their pairwise proximities into a DNA sequence library.

Comprehensive maps of mutations in healthy and diseased gastric tissue give clues about how cancer arises and could inform early-detection strategies.

Bacterial genomes still contain many hidden and uncharacterized genes. Using complementary Ribo-seq approaches, Froschauer, Svensson et al. here annotate start and stop codons ofCampylobacter jejuni, reporting a high-resolution translatome and identifying several novel small ORFs in this foodborne pathogen.

Selecting the appropriate Cas12a among the many orthologs for a given target sequence remains difficult. Here, Peng Chen et al. evaluate the activity and specificity of Cas12a variants and facilitate the selection of guide RNA and appropriate Cas12a candidates for gene editing.

In this Tutorial, the authors provide guidelines for quality control of whole-exome and whole-genome sequencing data for population-scale association analyses. They explain how to filter samples and variants, and compare commonly used software programs for quality control of sequencing data.

Advances in long-read sequencing are driving the implementation of these technologies for transcriptome profiling. The authors provide a comprehensive guide to long-read RNA sequencing, including experimental and computational tools, current applications, challenges and opportunities.

Long-read sequencing technologies can directly profile methylation modifications across the genome. In this Review, Fu et al. overview the long-read computational tools to identify and compare methylation signals, as well as tools that use these methylation signals to analyse cell-type diversity and gain additional genomic insights.

Uncalled4 is a toolkit for nanopore signal alignment, analysis and visualization allowing for performant detection and analysis of DNA and RNA modifications.

We introduce volumetric DNA microscopy, a technique that enables three-dimensional imaging of tissue morphology and gene expression in a single measurement. This feat is achieved by forming a huge intermolecular network of DNA barcodes within an intact specimen and encoding their pairwise proximities into a DNA sequence library.

Comprehensive maps of mutations in healthy and diseased gastric tissue give clues about how cancer arises and could inform early-detection strategies.

In individuals receiving an allogeneic haematopoietic cell transplant, stem cells in the bone marrow, which give rise to blood and immune cells, are replaced with those from a donor. Genome-sequencing analyses in donor–recipient pairs years after transplantation show an accelerated loss of clonal diversity in the blood stem cells of recipients compared with those of donors.

In this Tools of the Trade article, Goronzy (Guttman lab) describes the development of ChIP-DIP, a high-throughput, split-pool barcoding method that enables genome-wide profiling of hundreds of regulatory proteins, transforming our ability to study the regulation of gene activity across cell types and biological contexts.

Using a combination of single-cell RNA sequencing, T cell and B cell receptor sequencing, and mass cytometry analyses, we characterized the dynamics of peripheral immune cells across the human lifespan. Based on this resource, we present a single-cell immune aging clock to assess an individual’s immune status across different life stages.

Ayako Suzuki recalls two papers published in the early 2000s by the Functional Annotation of the Mammalian Genome (FANTOM) consortium and the Full-Length Long Japan (FLJ) project, which provided reference catalogues of full-length transcripts in mice and humans, respectively.