Authors : Manan Chandra

Volume/Issue : Volume 11 - 2026, Issue 5 - May

Google Scholar : https://tinyurl.com/4pz3p5xk

Scribd : https://tinyurl.com/22j8xy34

DOI : https://doi.org/10.38124/ijisrt/26May155

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Recent advances in long-read sequencing technologies have significantly expanded the diagnostic capabilities of next-generation sequencing (NGS) in oncology. While short-read sequencing has enabled large-scale genomic profiling, it remains limited in resolving structural variants, gene fusions, and complex genomic rearrangements that characterize tumor genomes. Long-read platforms now enable improved detection of these features, along with direct analysis of epigenetic modifications and transcript isoforms. In this review, we present a comprehensive and integrated overview of long-read sequencing technologies within the context of cancer diagnostics, spanning the full NGS workflow from sample preparation and quality control to sequencing, demultiplexing, and clinical interpretation. We highlight key applications in structural variant detection, liquid biopsy, transcriptomics, and precision oncology, while critically examining current limitations and outlining future directions for clinical translation.

References :

1. Alpern, D., Gardeux, V., Russeil, J., et al. (2019). BRB-seq: ultra-affordable high-throughput transcriptomics enabled by bulk RNA barcoding and sequencing. Genome Biology, 20, 71.
2. Amarasinghe, S.L., Su, S., Dong, X., et al. (2020). Opportunities and challenges in long-read sequencing data analysis. Genome Biology, 21, 30.
3. Bredenoord, A.L., et al. (2021). Automation in genomics and its impact on reproducibility. Nature Methods, 18, 104–110.
4. Chaisson, M.J.P., Sanders, A.D., Zhao, X., et al. (2019). Multi-platform discovery of haplotype-resolved structural variation. Nature Communications, 10, 1784.
5. Dorney, K., et al. (2023). Detection of gene fusions using long-read sequencing. Briefings in Bioinformatics, 24, bbac519.
6. Gansauge, M.T., and Meyer, M. (2020). Single-stranded DNA library preparation for highly degraded DNA. Nature Protocols, 15, 2041–2054.
7. Goodwin, S., McPherson, J.D., and McCombie, W.R. (2016). Coming of age: ten years of next-generation sequencing technologies. Nature Reviews Genetics, 17, 333–351.
8. Heitzer, E., Haque, I.S., Roberts, C.E.S., and Speicher, M.R. (2019). Current and future perspectives of liquid biopsies in genomics-driven oncology. Nature Reviews Genetics, 20, 71–88.
9. Jansson, L., et al. (2024). Assessment of DNA quality for whole genome library preparation. Analytical Biochemistry, 688, 115123.
10. Jennings, L.J., Arcila, M.E., Corless, C., et al. (2020). Guidelines for validation of next-generation sequencing–based oncology panels. The Journal of Molecular Diagnostics, 22, 341–365.
11. Lee, H., et al. (2022). Nanopore sequencing and methylation analysis. Nature Biotechnology.
12. Logsdon, G.A., Vollger, M.R., and Eichler, E.E. (2020). Long-read human genome sequencing and its applications. Nature Reviews Genetics, 21, 597–614.
13. Metzker, M.L. (2010). Sequencing technologies — the next generation. Nature Reviews Genetics, 11, 31–46.
14. Muir, P., et al. (2020). The real cost of sequencing: scaling computation to keep pace with data generation. Genome Biology, 21, 53.
15. Nurk, S., Koren, S., Rhie, A., et al. (2022). The complete sequence of a human genome. Science, 376, 44–53.
16. O’Neill, K., et al. (2024). Long-read sequencing of cancer genomes reveals structural complexity. Cell Genomics.
17. Pignatta, S., et al. (2025). Comparative analysis of library preparation approaches for degraded samples. Scientific Reports, 15, 12992.
18. Rebello, R., et al. (2025). Whole genome and transcriptome sequencing improves cancer diagnostics. Nature Communications.
19. Robins, H. (2013). Immunosequencing: applications of immune repertoire deep sequencing. Current Opinion in Immunology, 25, 646–652.
20. Sanger, F., Nicklen, S., and Coulson, A.R. (1977). DNA sequencing with chain-terminating inhibitors. PNAS, 74, 5463–5467.
21. Shafin, K., Pesout, T., Lorig-Roach, R., et al. (2020). Nanopore sequencing and deep learning variant calling. Nature Biotechnology.
22. Sung, H., Ferlay, J., Siegel, R.L., et al. (2021). Global cancer statistics 2020. CA: A Cancer Journal for Clinicians, 71, 209–249.
23. Szakállas, N., et al. (2024). Long-read sequencing in clinical genomics. Pathology & Oncology Research.
24. Tsui, D.W.Y., et al. (2025). Fragmentomics and cancer detection using cfDNA. Cancer Cell.
25. van Dijk, E.L., Jaszczyszyn, Y., and Thermes, C. (2023). The long-read sequencing revolution. Trends in Genetics, 39, 3–16.
26. Wan, J.C.M., Massie, C., Garcia-Corbacho, J., et al. (2017). Liquid biopsies in cancer. Nature Reviews Cancer, 17, 223–238.
27. Wenger, A.M., Peluso, P., Rowell, W.J., et al. (2019). Accurate circular consensus long-read sequencing. Nature Biotechnology.