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PacBio HiFi sequencing technology continues to be the tool of choice for genomics professionals working at the forefront of discovery, enabling them to pursue new avenues of exploration across diverse domains of biology.
In this edition of our Powered by PacBio blog series, we highlight scientific papers from the month of February 2024. These intriguing publications highlight the power of PacBio sequencing for unraveling the complexities of rare disease, cancer transcriptomics, agrigenomics, and more.
Jump to topic:
Cancer transcriptomics Rare disease Neurobiology/Iso-Seq Agrigenomics
Cancer transcriptomics
Full-length isoform concatenation sequencing to resolve cancer transcriptome complexity
In this paper, researchers at Nationwide Children’s Hospital and Ohio State University present their work on the identification of differential full-length isoform expression in a pediatric diffuse midline glioma as compared to adjacent non-malignant tissue.
Key takeaways:
• The team used a modified version of MAS-Seq which is the core chemistry that drives the PacBio Kinnex kits.
• The use of PacBio full-length RNA sequencing led to the discovery of an isoform of the SPARC gene that was expressed >10,000-fold higher than in the adjacent non-malignant tissue.
• The researchers were also able to use PacBio long reads to detect several cancer-specific novel isoforms, which “highlight the importance of long-read sequencing for characterization of complex tumor transcriptomes”.
Rare disease
Novel syndromic neurodevelopmental disorder caused by de novo deletion of CHASERR, a long noncoding RNA
In this preprint, an international team shows for the first time “that de novo structural variants facilitated by Alu-mediated non-allelic homologous recombination led to deletion of a non-coding element (the lncRNA CHASERR ) to cause a rare syndromic neurodevelopmental disorder”. The team used PacBio long-read sequencing to resolve the SV and identify three adjacent de novo SNPs in cis with the deletion.
Key takeaway:
• “This work highlights the need to carefully evaluate other lncRNAs, particularly those upstream of genes associated with Mendelian disorders.”
Neurobiology/Iso-Seq method
Full-length transcript sequencing traces the brain isoform diversity in house mouse natural populations
In this preprint a team of scientists from Germany and China applied PacBio full-length RNA sequencing (Iso-Seq) to 48 individuals from outbred mouse populations and subspecies, representing “the largest full-length high-quality isoform catalog at the population level to date” .
Key takeaways:
• The authors note that “complexity and diversity of alternative isoforms in natural populations remains largely unexplored”.
• >117,000 distinct transcripts were identified in the study, “of which only 51% were previously annotated ”.
• In interpreting their results, the team found that “ancient house-keeping genes are the major source to the overall isoform diversity, and the recruiting of alternative first exon plays the dominant role in generating new isoforms .”
• Conclusion: “Given that our data allow to distinguish between population-specific isoforms and isoforms that are conserved across multiple populations, it is possible to refine the annotation of the reference mouse genome to a set of about 40,000 isoforms that should be most relevant for comparative functional analysis across species.”
Agrigenomics
Adaptive diversification through structural variation in barley
In this preprint an international collaboration of scientists from 23 global institutions presents a pangenome of barley comprising HiFi assemblies from 76 wild and domesticated genomes .
Key takeaways:
• The completion of this pangenome expands the “catalogue of sequence variation in the crop” that “includes structurally complex loci”.
• Such loci include those “…involved in disease resistance, plant architecture, nutrient release, and trichome development.
• Conclusion: “Our findings indicate that rapid evolution at structurally complex loci may have helped crop plants adapt to new selective regimes in agricultural ecosystems .”
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