Next Generation Sequencing: What are Challenges and Solutions for Target Enrichment?

Powerful, fast computers with parallel processing capabilities helped to usher in the era of next generation sequencing in genetics. As the technology improves and grows less expensive to produce at scale, more scientists and researchers can avail themselves of these vital tools. We are now able to sequence a person’s genome and read the details to help discover ways to improve an individual’s health outlook.

But it still is costly to perform NGS scans, even if it’s just covering part of a person’s genes and not the entire genome.

Under these circumstances, technicians will work to improve their target enrichment capabilities. Target enrichment is a way to focus on just the sections of the genes that you are most interested in, so you can examine them in greater detail or obtain more samples at a lower budget.

Next Generation Sequencing and Target Enrichment

Researchers have two primary ways to engage in target enrichment as they study genetic sequences. According to commentary by Steven Henck, PhD, Vice President, R&D at Integrated DNA Technologies in Bio-IT World, the most common approaches are hybrid capture-based enrichment and amplicon-based enrichment.

With hybrid-capture, you use hybridizing probes in a panel to examine only the regions you are most interested in. The DNA fragments that are not bound up in the analysis simply wash away. With amplicon-based target enrichment, a scientist will employ PCR panels in a panel, and then purify the results before sequencing.

Hybrid captures are suited for occasions when you are working with novel targets or those that are large and variable. A technician needs to use additional primers when there are more regions of interest to explore. So while amplicon-based enrichment won’t do well under these circumstances, the hybrid method allows you to disregard sequences you didn’t want to study, so it’s more efficient.

Per Bio-IT World, cancer biomarker discovery is a good example of the utility of hybrid capture approaches. Cancer genes develop when DNA breakpoints are the sites of gene fusion. It’s hard to sequence these genetic sequences, which have the potential to become cancer-producing. A hybrid approach lets you use next generation sequencing to sequence the genes across the point of fusion.

As Henck noted, “Target enrichment is a useful tool for streamlining NGS by focusing on regions of interest and cutting away the clutter of sequencing areas of the genome which may not be of interest. This allows for more samples to be sequenced at greater depth.”

COVID-19 prevention efforts cry out for more sequencing of the virus as people fall ill. It’s vital for discovering new variants as well as helping public health professionals determine which regions of a country have which forms of the virus and in what proportion, which is needed when developing new vaccines and boosters.

A significant example of using amplicon-based enrichment to great effect in NGS is scientists scanning SARS-CoV-2 (COVID-19) variants. Using primers that pair with overlapping coverage makes it easier for researchers to sequence new variants (based on their first work detecting variants such as Omicron and Delta, and then amplifying those genetic sequences).

Speeding Up Next Generation Sequencing Projects With Target Enrichment

Since scientists have to work with limited materials and finite budgets, having more tools at their disposal to accomplish next generation sequencing more quickly and efficiently is essential to their NGS projects.

The costs of sequencing being what they are means that medical researchers need an affordable way to examine genetic sequences without breaking their entire laboratory budget. So efforts such as target enrichment will be a useful way to shore up the gap between the competition for more time and money in genetic-based studies.

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