Long-read sequencing powers a more complete reading of genomic information.

To large-scale projects and individual labs, long-read sequencing has delivered new vistas and long wish lists for this technology’s future.

The year 2022 will be remembered as the turning point for accurate long-read sequencing, which now establishes the gold standard for speed and accuracy at competitive costs. We discuss the key bioinformatics techniques needed to power long reads across application areas and close with our vision for long-read sequencing over the coming years.

As long-read sequencing technologies continue to advance, the possibility of obtaining maps of DNA and RNA modifications at single-molecule resolution has become a reality. Here we highlight the opportunities and challenges posed by the use of long-read sequencing technologies to study epigenetic and epitranscriptomic marks and how this will affect the way in which we approach the study of health and disease states.

DeePiCt (deep picker in context) is a versatile, open-source deep-learning framework for supervised segmentation and localization of subcellular organelles and biomolecular complexes in cryo-electron tomography.

This work presents a computational framework, COMMOT, to spatially infer cell–cell communication from transcriptomics data based on a variant of optimal transport (OT).

An optimized pipeline for improved inference and analysis of structural variants (SVs) has been developed, which uses Iris for refining breakpoints and sequences, and Jasmine for comparing SV calls at population scale.

Hybrid Unmixing offers enhanced imaging of multiplexed fluorescence labels, enabling longitudinal imaging of multiple fluorescent signals with reduced illumination intensities.

A computational pipeline for haplotype-aware pantranscriptome analysis has been developed, which enables spliced pangenome graph construction, RNA sequencing data alignment, and estimation of haplotype-specific transcript expression levels.

Cryogenic correlated light, ion and electron microscopy (cryo-CLIEM) integrates three-dimensional confocal microscopy with focused ion beam–scanning electron microscopy for efficient preparation of lamellae containing target structures for in situ structural biology with cryo-electron tomography.

Dramatic advances in protein structure prediction have sparked debate as to whether the problem of predicting structure from sequence is solved or not. Here, I argue that AlphaFold2 and its peers are currently limited by the fact that they predict only a single structure, instead of a structural distribution, and that this realization is crucial for the next generation of structure prediction algorithms.

Mechanoimmunology methods help dissect the mechanical forces within the immune system.

CRISPR systems can be leveraged to direct recombinases to integrate gene-sized DNA sequences.

Strategies to overcome poor reproducibility in MRI studies are needed.

In vitro models and single-cell atlases help uncover the mysteries of human embryogenesis.