See how the Chaisson lab created a new method to characterize human VNTR variation with PacBio long-read sequencing.
Structural variants are hard to find with short-read sequencing methods
At present, most genomic researchers worldwide use short-read sequencing methods based on aging sequencing-by-synthesis (SBS) technology. However, short reads are unable to detect SVs effectively due to their large size and potentially repetitive nature, resulting in a critical knowledge gap in human genomics. Very accurate long reads – such as those generated by the new high-throughput Revio system – allow researchers to tackle this information gap head-on by enabling access to the entirety of the human genome, including difficult SVs.
Variable number tandem repeats (VNTRs) are a type of SV that have historically been problematic to study. Mark Chaisson of the University of Southern California has studied VNTR analysis methods extensively and points out that the low-to-no-coverage of tandem repeat regions by short read data means that “enormous effort” is required to try and estimate motifs. Because of this seemingly insurmountable limitation created by short reads, the Chaisson lab uses PacBio long-read sequencing data to study VNTRs. Their research resulted in the creation of a dedicated tool for finding them – called VAMOS, which stands for VNTR Annotation using Efficient Motif Sets.
Use VAMOS to efficiently discover VNTRs with PacBio long reads
Interested into learning more about VAMOS including the nuts and bolts of how the tool works – and the new biology that you can find with it?
Chapters include:
Why HiFi reads are the best choice for SV analysis
What could potentially be found with short-read data
Moving to a world where we can get digital counts of motifs
How the VAMOS pipeline is set up
Hidden structural variation is waiting to be revealed
Understanding the human genome is an ongoing pursuit that has the potential to revolutionize how we understand human health. One promising frontier of discovery in human genomics is the identification and understanding of structural variants (SVs). SVs are differences in DNA structure, ranging from small deletions or insertions to larger-scale alterations that can involve the gain or loss of entire chromosomes.
Identifying new SVs, such as variable number tandem repeats (VNTRs) and correctly connecting them to observable traits has the potential to significantly improve our understanding of the genetic basis of diseases and inform targeted treatments.
The implications of identifying and understanding SVs are far-reaching and could have a significant impact on how human health is approached around the world. Studying SVs within the human genome is an exciting area of research that holds great promise for advancing our understanding of human biology and improving global health outcomes.
With the power of tools like VAMOS and the accuracy and reliability of HiFi reads, we’re excited to see what discoveries are waiting to be uncovered.