Selective Sequencing with Nanopore Technology: Adaptive Sampling as a Real-Time Enrichment Strategy for Nuclear DNA

Third-generation sequencing methods like Oxford Nanopore are opening new doors in genomics by enabling long-read DNA sequencing in real time. Adaptive sampling is one of the optional features offered by Nanopore sequencing, allowing selective enrichment of genomic regions of interest during the sequencing process. This approach relies on real-time analysis of DNA fragments: when a fragment aligns to a target region, it is sequenced; otherwise, it is actively ejected from the flow cell. This helps focusing on the sequencing the targeted parts of the DNA. This thesis outlines the technical principles of adaptive sampling and identifies scenarios in which it can be beneficial for enrichment, such as large nuclear gene panels. The project investigates datasets generated during a human genetics internship, where adaptive sampling was used to target selected areas of the nuclear genome. Graphical results from genes such as TWNK, OTOA, and RRM2B demonstrate differential enrichment performance depending on genomic context and design parameters. These findings highlight adaptive sampling's potential as a flexible tool in targeted sequencing workflows, while also underscoring its limitations—including variable efficiency, high computational demands, and dependence on library quality. In conclusion, adaptive sampling represents a promising but still maturing enrichment strategy that requires careful evaluation for each specific use case.