The article presents a study on the accurate detection of complex structural variations (SVs) using single molecule sequencing technologies. The authors introduce two open-source tools, NGMLR and Sniffles, which are designed for long-read alignment and SV identification. NGMLR is a fast and accurate aligner for long-reads, while Sniffles is used to detect all types of SVs, including complex nested events. The tools are tested on various datasets, including healthy and cancerous human genomes, and are shown to significantly improve SV detection accuracy compared to short-read methods. The study also highlights the challenges of long-read sequencing, such as high error rates, and demonstrates how NGMLR and Sniffles can filter false events and operate with low coverage. The results show that these tools can detect thousands of novel variants and reduce sequencing and computational costs, making long-read sequencing more feasible for clinical and research applications. The study also compares the performance of PacBio and Oxford Nanopore sequencing technologies for SV analysis, showing that both have strengths and limitations. Overall, the study demonstrates the potential of long-read sequencing to significantly advance the understanding of structural variations in the human genome.The article presents a study on the accurate detection of complex structural variations (SVs) using single molecule sequencing technologies. The authors introduce two open-source tools, NGMLR and Sniffles, which are designed for long-read alignment and SV identification. NGMLR is a fast and accurate aligner for long-reads, while Sniffles is used to detect all types of SVs, including complex nested events. The tools are tested on various datasets, including healthy and cancerous human genomes, and are shown to significantly improve SV detection accuracy compared to short-read methods. The study also highlights the challenges of long-read sequencing, such as high error rates, and demonstrates how NGMLR and Sniffles can filter false events and operate with low coverage. The results show that these tools can detect thousands of novel variants and reduce sequencing and computational costs, making long-read sequencing more feasible for clinical and research applications. The study also compares the performance of PacBio and Oxford Nanopore sequencing technologies for SV analysis, showing that both have strengths and limitations. Overall, the study demonstrates the potential of long-read sequencing to significantly advance the understanding of structural variations in the human genome.