Long-Read Sequencing Methodology

Algorithms for transcript isoforms, structural variation, and regulatory disruption from PacBio and ONT long reads.

We develop computational methods for long-read RNA-seq and DNA-seq that resolve complex transcript isoforms, fusion transcripts, structural variation, and regulatory disruption that are difficult to capture with short-read assays. Our methods span bulk and single-cell modalities and target both reference-based and assembly-based representations of the genome.

Lab-led contributions include CTAT-LR-Fusion for accurate fusion transcript identification at bulk or single-cell resolution (Qin et al., 2025), somatic structural variant calling that combines pangenome and de novo personal genome assembly (Qin et al., 2025), and diploid donor-specific assemblies (DSAs) as cancer reference genomes that recover over 20% additional somatic SVs missed on GRCh38 or CHM13 (Zhang et al., 2025). Related publications in this space include colorSV, a long-range somatic SV caller that uses matched tumor-normal co-assembly graphs to recover translocations and other complex events (Le et al., 2025); LongcallD, a local-haplotagging variant caller that jointly calls and phases small, structural, and low-fraction mosaic variants from PacBio HiFi and ONT reads (Gao et al., 2026); and FuFiHLA, a tool for full-field HLA allele typing directly from PacBio HiFi and ONT long reads (Hu et al., 2026). Together these tools improve sensitivity and precision for clinically relevant variation that short-read pipelines routinely miss.

References

2026

  1. bioRxiv
    LongcallD: joint calling and phasing of small, structural and mosaic variants from long reads
    Yan Gao, Wen-Wei Liao, Qian Qin, and 2 more authors
    bioRxiv, Mar 2026
  2. Bioinformatics
    FuFiHLA: A tool for full-field HLA typing from long-read data
    Jingqing Hu, Qian Qin, Heng Li, and 1 more author
    Bioinformatics, May 2026

2025

  1. Genome Res
    Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution
    Qian Qin, Victoria Popic, Kirsty Wienand, and 11 more authors
    Genome Research, Apr 2025
  2. bioRxiv
    Improving long-read somatic structural variant calling with pangenome and de novo personal genome assembly
    Qian Qin, Jakob Heinz, and Heng Li
    bioRxiv, Oct 2025
  3. bioRxiv
    Diploid donor-specific assembly enhances somatic structural variant detection in cancer genomes
    Yuwei Zhang, Han Qu, Qian Qin, and 2 more authors
    bioRxiv, Oct 2025
  4. GPB
    colorSV: Long-range Somatic Structural Variation Calling from Matched Tumor-normal Co-assembly Graphs
    M K Le, Qian Qin, and Heng Li
    Genomics, Proteomics & Bioinformatics, Sep 2025