A team of Vanderbilt researchers has developed a novel tool in the detection and analysis of structural variants (SVs) in human genomes that could potentially transform genomic analysis and precision medicine. The research was recently published in Nature Communications.

Structural variants (SVs)—which include deletions, insertions, translocations, duplications, and inversions—play a critical role in human genetic diversity and disease. However, despite advancements in long-read sequencing technologies, accurately identifying these complex genomic alterations has remained a formidable challenge—until now.

The Vanderbilt team has created VolcanoSV, which stands out from previous methodologies by generating a high-quality haplotype-resolved diploid assembly. The process constructs two separate, continuous genome sequences representing the two distinct sets of chromosomes (haplotypes) inherited from each parent in a diploid (human) organism.

This cutting-edge pipeline not only enhances the precision and recall of SV detection, but also significantly improves the accuracy of genotyping across a wide range of datasets, including those with low sequencing coverage. In rigorous testing against existing state-of-the-art tools, VolcanoSV demonstrated superior performance metrics, including higher F1 scores, recall, precision, and genotype concordance.

"Our goal with VolcanoSV was to address the limitations of current SV detection methods, especially in complex and clinically relevant genomic regions," said Xin Maizie Zhou, one of the lead researchers on the project and an assistant professor of biomedical engineering and computer science at Vanderbilt. "VolcanoSV's ability to accurately detect and phase structural variants, even in challenging low-coverage datasets, makes it an invaluable resource for advancing personalized medicine and human genomics research."

By enabling more accurate characterization of structural variants, researchers said VolcanoSV opens new avenues for understanding the genetic underpinnings of diseases such as cancer and neurological disorders.

"The robust performance of VolcanoSV across various sequencing platforms and its applicability to both research and clinical settings underscore its potential to transform genomic analysis and precision medicine," according to the team, which also includes Vanderbilt's Can Luo and Yichen Henry Liu.