Cancer is a complex disease, and understanding its full picture of genetic causes requires equally sophisticated tools. One technology that’s helping researchers uncover previously hidden changes in cancer genomes is long-read sequencing. In a recent two-part webinar series, experts Dr. Nathan Blewett and Dr. Leif Schauser shared practical insights into how long-read sequencing and target enrichment workflows are being used to both generate high-quality long reads and analyze and interpret them effectively.
Part 1: Navigating cancer genome complexities with long-read sequencing
In this compelling session, Dr. Nathan Blewett, a scientist at QIAGEN, explained how long-read sequencing works and why it's important.
Traditional DNA sequencing methods read short fragments of DNA – usually a few hundred base pairs long. These work well for many applications but often miss large or complex structural changes in the genome. In contrast, long-read sequencing reads DNA fragments that can span thousands of base pairs. This allows scientists to detect larger rearrangements or mutations that may play a key role in cancer development.
Nathan described how the QIAseq xHYB long-read panels are designed to make this type of sequencing easier and more accurate. Some key points:
- The system uses special “probes” to capture specific regions of the genome for sequencing
- It works with different ways of breaking DNA into fragments – either using enzymes or mechanical shearing – depending on the sample and lab setup
- It includes chemistry that’s fine-tuned to produce even coverage across the targeted regions, even in difficult areas with high GC content
He also stressed that the system is tightly integrated, meaning it’s important to use the whole workflow as designed. Swapping in third-party components could affect results.
Another advantage is that researchers can add custom probes to existing panels. This allows them to target additional genes or regions without starting from scratch. It's a practical feature for cancer studies, where the list of genes of interest can grow as new discoveries are made.
Part 2: Decoding long reads with powerful bioinformatics tools
Sequencing is only half the story. Once scientists have the data, they need tools to interpret it. In the second webinar, Dr. Leif Schauser, a product manager at QIAGEN, walked through the bioinformatics side of things.
He introduced the QIAGEN CLC Genomics Workbench, a software platform that helps researchers:
- Assemble full genomes using long reads
- Identify genetic variants
- Visualize the data and generate reports
Unlike some systems that require high-powered hardware, this software runs efficiently on standard computers. It also offers features that are important for regulated labs, like audit trails and locked workflows.
Leif shared examples of how the software performed on real data sets, including the detection of large deletions in cancer-related genes like TSC2 and DCC. These are cases where short-read sequencing might miss the full extent of the mutation, but long-read sequencing combined with good analysis tools can provide a much clearer picture.
Why it matters
Cancer is often driven by changes in the genome that are hard to detect with standard tools. Long-read sequencing helps fill in those gaps. Together with strong bioinformatics support, researchers can now:
- Identify complex mutations more easily
- Customize their experiments as new questions arise
- Get more reliable results for challenging samples
This combination of new sequencing methods and advanced software is giving scientists the tools they need to dig deeper into cancer biology – and potentially find better ways to diagnose and treat the disease.
Further reading and resources
If you’d like to explore the technology and tools discussed in more detail, here are some useful links: