Biotech Connector showcases advances in next-generation sequencing

The final Biotech Connector of 2024 focused on advances and uses of next-generation sequencing (NGS) by three organizations in the Frederick, Md, region.  

NGS can rapidly sequence DNA and RNA, enabling scientists to study genetic variation. It’s called “next generation” because it represents a substantial leap forward over older methods. NGS was first launched in 2000 but has been continually advanced since. 

The Biotech Connector is a quarterly networking and speaker series, hosted by the Frederick National Laboratory for Cancer Research and the Frederick County Chamber of Commerce, to bring together life science professionals for an inside look at local advances and to network. The advantages of NGS are “throughput, speed, and scale” explained Olena Lar, Ph.D., senior director of research and development at CIAN Diagnostics and one of the event’s three speakers. NGS achieves this by investigating millions of fragments of DNA or RNA simultaneously. 

Sequencing technologies  

Bao Tran, M.S., director of operations at the Sequencing Facility at the Frederick National Laboratory, discussed the different sequencing technologies available in his laboratory. The Sequencing Facility has served more than 260 National Institutes of Health investigators in the past year. The team tailors the technology and approach taken to address each project. 

The first decision is to choose between short-read sequencing, the most common type of NGS, or long-read sequencing (also known as third-generation sequencing). Tran explained that long-read sequencing uses longer fragments of DNA (or RNA), hence the name. As a result, long read can capture more complex structural variations from the native DNA (or RNA) than short read. However, long read has a higher error rate, higher cost per DNA base, and longer run time than other sequencing measures. 

Next, his team decides which sequencing platform best suits the project. The standard instrument in his laboratory can perform four million reads per run, while the most advanced can do 50 billion reads per run, with higher operating costs.  

Tran also noted the extent to which NGS has advanced the sequencing field.  

“It cost about $1 billion and 10 years to complete the first human genome,” he said. “With [modern NGS instruments], we can do 128 human genomes in 48 hours.”  

Making genetic testing more accessible 

Lar discussed the importance of genetic testing and how the technology is increasingly being used to make healthcare treatment decisions. She also stressed that minor genetic changes can be clinically-relevant.  

“When you look at the human genome, 99.6% is shared" among all humans, Lar said. “Only 0.4% is variable, and this is what we are evaluating for genetic testing. A majority of this variance, they consist of a single nucleotide variance. It’s just the one letter replacement in your DNA sequence: insertions or deletions.” 

Lar wants to make genetic testing more affordable and available, particularly for smaller laboratories. She considers factors such as cost per sample, portability, and usability in field settings. She presented validation work comparing two sequencing platforms (Illumina and Oxford Nanopore) and found that after optimization, their resolutions compared favorably for certain clinical uses. The Oxford Nanopore system was simpler, faster, and less expensive to use than other assay systems. Her team is now planning a full-scale study to validate their preliminary results.  

Improving the entire process 

Samuel Rulli, Ph.D., associate director of global product management at QIAGEN, also seeks to make NGS more accessible and easier to use. He stressed that each step in the process is important, starting with sample preparation and ending with data analysis and interpretation. 

“It is the whole workflow we’re concerned with,” Rulli said.  

He also presented a library kit and workflow that enables NGS to investigate DNA and RNA together, known as total nucleic acid analysis. This approach requires less total material than performing separate analyses for DNA and RNA, allowing investigators to maximize their use of small samples. This is particularly important in cancer research, where biopsies may assess small biomass samples. 

Join us in February  

Stay tuned for the dates of our 2025 series. The next event will be in February. Join the mailing list to ensure you don’t miss it!