Standard shotgun mNGS is a powerful tool that looks at all DNA in a sample without bias. However, a recent narrative review suggests that adding specific enrichment steps could help find certain pathogens more easily. These methods include PCR-based enrichment, CRISPR-Cas9 enrichment, and others like molecular inversion probes or nanopore adaptive sequencing.
The review looked at how these new techniques compare to the standard shotgun approach. They examined factors like cost, sensitivity, and how easy it is to use them in a hospital lab. The goal is to guide doctors and lab staff on how to optimize their diagnostic workflows for better patient care.
But there is a trade-off to consider. Using these enrichment steps changes the nature of the test. It compromises the hypothesis-free nature and breadth of the standard shotgun method. This means the test no longer looks at everything equally, which is a significant limitation for a method that prides itself on being unbiased.
