160: Long reads meet single-cell omics

Wen L et al., Trends in Genetics - This review surveys the integration of single-molecule long-read sequencing (SMS) with single-cell genomics, epigenomics and transcriptomics, describing platforms, methods and the new biological 'dark matter' now accessible at single-cell resolution. Key terms: single-cell sequencing, long-read sequencing, alternative splicing, structural variation, transposable elements. Study Highlights:SMS platforms (PacBio HiFi and Oxford Nanopore) have improved accuracy and enable direct full-length cDNA sequencing to resolve alternative splicing and isoforms in individual cells. Long reads substantially improve detection of repetitive elements, structural variants, ecDNAs and enable chromosome-scale haplotype phasing from small cell numbers. SMS-based single-cell epigenome methods capture allele-specific DNA methylation, histone marks, TF binding and higher-order 3D chromatin interactions, including within repetitive regions. New single-cell long-read methods (for transcriptome, genome and multiple epigenomic layers) are expanding capabilities but remain constrained by capture efficiency, cost and amplification artifacts. Conclusion:SMS-based long-read single-cell omics opens access to genomic and epigenomic 'dark matter'—full-length isoforms, repeats, SVs and allele-specific regulation—and points toward future single-cell de novo assemblies, multi-omics and spatial long-read applications. Music:Enjoy the music based on this article at the end of the episode. Article title:Single-cell omics sequencing technologies: the long-read generation First author:Wen L Journal:Trends in Genetics DOI:10.1016/j.tig.2025.07.012 Reference:Wen L. and Tang F. Single-cell omics sequencing technologies: the long-read generation. Trends in Genetics. 2025. https://doi.org/10.1016/j.tig.2025.07.012 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/the-longread-leap-in-singlecell-omics